US 12,168,767 B2
Modified double-stranded RNA agents
Martin Maier, Cambridge, MA (US); Don Foster, Cambridge, MA (US); Stuart Milstein, Cambridge, MA (US); Satya Kuchimanchi, Cambridge, MA (US); Vasant Jadhav, Cambridge, MA (US); Kallanthottathil Rajeev, Cambridge, MA (US); Muthiah Manoharan, Cambridge, MA (US); and Rubina Parmar, Cambridge, MA (US)
Assigned to Alnylam Pharmaceuticals, Inc., Cambridge, MA (US)
Filed by ALNYLAM PHARMACEUTICALS, INC., Cambridge, MA (US)
Filed on Dec. 22, 2022, as Appl. No. 18/145,238.
Application 18/145,238 is a continuation of application No. 17/941,436, filed on Sep. 9, 2022.
Application 17/941,436 is a continuation of application No. 17/847,550, filed on Jun. 23, 2022, granted, now 11,549,109.
Application 17/847,550 is a continuation of application No. 17/523,240, filed on Nov. 10, 2021, granted, now 11,427,822, issued on Aug. 30, 2022.
Application 17/523,240 is a continuation of application No. 17/479,617, filed on Sep. 20, 2021, abandoned.
Application 17/479,617 is a continuation of application No. 16/693,683, filed on Nov. 25, 2019, granted, now 11,401,517, issued on Aug. 2, 2022.
Application 16/693,683 is a continuation of application No. 16/384,644, filed on Apr. 15, 2019, granted, now 10,612,027, issued on Apr. 7, 2020.
Application 16/384,644 is a continuation of application No. 16/272,721, filed on Feb. 11, 2019, granted, now 10,612,024, issued on Apr. 7, 2020.
Application 16/272,721 is a continuation of application No. 15/504,855, granted, now 10,233,448, issued on Mar. 19, 2019, previously published as PCT/US2015/045407, filed on Aug. 14, 2015.
Claims priority of provisional application 62/093,919, filed on Dec. 18, 2014.
Claims priority of provisional application 62/083,744, filed on Nov. 24, 2014.
Claims priority of provisional application 62/039,507, filed on Aug. 20, 2014.
Prior Publication US 2023/0183701 A1, Jun. 15, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07H 21/02 (2006.01); C12N 15/11 (2006.01); C12N 15/113 (2010.01)
CPC C12N 15/113 (2013.01) [C12N 15/111 (2013.01); C12N 2310/14 (2013.01); C12N 2310/313 (2013.01); C12N 2310/32 (2013.01); C12N 2310/3231 (2013.01); C12N 2310/332 (2013.01); C12N 2310/335 (2013.01); C12N 2310/344 (2013.01); C12N 2310/346 (2013.01); C12N 2310/351 (2013.01); C12N 2310/533 (2013.01); C12N 2320/51 (2013.01); C12N 2320/52 (2013.01)] 25 Claims
 
1. A double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene, comprising a sense strand and an antisense strand complementary to at least one portion of a mRNA of the target gene, each strand having 14 to 40 nucleotides and forming a duplex region of 14 to 40 base pairs, wherein
the antisense strand comprises 2′-fluoro modifications only at positions 2, 6, 14, and 16 of the antisense strand, counting from the 5′-end of the antisense strand; and
each nucleotide of the antisense strand is independently modified with a modification selected from the group consisting of an acyclic nucleotide, LNA, HNA, CeNA, 2′-methoxyethyl, 2′-O-methyl, 2′-O-allyl, 2′-C-allyl, 2′-deoxy, 2′-fluoro, 2′-O-N-methylacetamido (2′-O-NMA), a 2′-O-dimethylaminoethoxyethyl (2′-O-DMAEOE), 2′-O-aminopropyl (2′-O-AP), and 2′-ara-F.