	US 12,071,619 B2
	SERPINA1 iRNA compositions and methods of use thereof
Alfica Sehgal, Medford, MA (US); Klaus Charisse, Acton, MA (US); Brian Bettencourt, Groton, MA (US); Martin A. Maier, Belmont, MA (US); Kallanthottathil G. Rajeev, Wayland, MA (US); Gregory Hinkle, Cambridge, MA (US); and Muthiah Manoharan, Weston, MA (US)
Assigned to Alnylam Pharmaceuticals, Inc., Cambridge, MA (US)
Filed by Alnylam Pharmaceuticals, Inc., Cambridge, MA (US)
Filed on Jan. 5, 2021, as Appl. No. 17/141,275.
Application 17/141,275 is a continuation of application No. 16/008,461, filed on Jun. 14, 2018, granted, now 10,920,223.
Application 16/008,461 is a continuation of application No. 15/399,820, filed on Jan. 6, 2017, granted, now 10,030,244, issued on Jul. 24, 2018.
Application 15/399,820 is a continuation of application No. 14/284,745, filed on May 22, 2014, granted, now 9,574,192, issued on Feb. 21, 2017.
Claims priority of provisional application 61/989,028, filed on May 6, 2014.
Claims priority of provisional application 61/979,727, filed on Apr. 15, 2014.
Claims priority of provisional application 61/898,695, filed on Nov. 1, 2013.
Claims priority of provisional application 61/826,125, filed on May 22, 2013.
Prior Publication US 2021/0317452 A1, Oct. 14, 2021
Int. Cl. C07H 21/02 (2006.01); A61K 31/712 (2006.01); A61K 31/713 (2006.01); C07H 21/04 (2006.01); C12N 15/113 (2010.01)

CPC C12N 15/113 (2013.01) [A61K 31/712 (2013.01); A61K 31/713 (2013.01); C12N 2310/11 (2013.01); C12N 2310/14 (2013.01); C12N 2310/315 (2013.01); C12N 2310/32 (2013.01); C12N 2310/321 (2013.01); C12N 2310/331 (2013.01); C12N 2310/332 (2013.01); C12N 2310/343 (2013.01); C12N 2310/344 (2013.01); C12N 2310/346 (2013.01); C12N 2310/351 (2013.01); C12N 2320/32 (2013.01); C12N 2320/34 (2013.01); C12N 2320/51 (2013.01); C12N 2330/30 (2013.01)]

18 Claims

1. A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of serine peptidase inhibitor, clade A member 1 (Serpina1) in a cell,

wherein said dsRNA agent comprises a sense strand and an antisense strand forming a double-stranded region,

wherein each strand is independently 19-30 nucleotides in length,

wherein said antisense strand comprises at least 19 contiguous nucleotides differing by no more than 3 nucleotides from any one of the antisense strand nucleotide sequences selected from the group consisting of

5′-UGGUAUUUUGUUCAAUCAUUAAG-3′ (SEQ ID NO:131);

5′-UUUUGUUCAAUCAUUAAGAAGAC-3′ (SEQ ID NO:133);

5′-AGACUUGGUAUUUUGUUCAAUCA-3′ (SEQ ID NO:135);

5′-AUUUUGUUCAAUCAUUAAGAAGA-3′ (SEQ ID NO: 137);

5′-AUUAAGAAGACAAAGGGUUUGUU-3′ (SEQ ID NO: 139);

5′-UGUUCAAUCAUUAAGAAGACAAA-3′ (SEQ ID NO: 141);

5′-AUCAUUAAGAAGACAAAGGGUUU-3′ (SEQ ID NO: 148);

5′-GAGACUUGGUAUUUUGUUCAAUC-3′ (SEQ ID NO: 150);

5′-AAGACAAAGGGUUUGUUGAACUU-3′ (SEQ ID NO: 152);

5′-AAGAGGGGAGACUUGGUAUUUUG-3′ (SEQ ID NO: 154);

5′-AGACAAAGGGUUUGUUGAACUUG-3′ (SEQ ID NO: 157);

5′-UUGGUAUUUUGUUCAAUCAUUAA-3′ (SEQ ID NO: 160);

5′-GACUUGGUAUUUUGUUCAAUCAU-3′ (SEQ ID NO: 179); and

5′-UGGGAUUCACCACUUUUCCCAUG-3′ (SEQ ID NO: 195),

wherein all of the nucleotides of said sense strand and all of the nucleotides of said antisense strand comprise a nucleotide modification, and

wherein at least one strand is conjugated to a ligand which is one or more GalNAc derivatives.