US 12,221,607 B2
Multi-targeted single entity conjugates
Vasant Jadhav, Cambridge, MA (US); Martin Maier, Cambridge, MA (US); Ivan Zlatev, Cambridge, MA (US); Akin Akinc, Cambridge, MA (US); Kallanthottathil G. Rajeev, Cambridge, MA (US); Jayaprakash K. Nair, Cambridge, MA (US); Pachamuthu Kandasamy, Cambridge, MA (US); and Muthiah Manoharan, Cambridge, MA (US)
Assigned to ALNYLAM PHARMACEUTICALS, INC., Cambridge, MA (US)
Filed by ALNYLAM PHARMACEUTICALS, INC., Cambridge, MA (US)
Filed on Feb. 22, 2021, as Appl. No. 17/181,870.
Application 17/181,870 is a division of application No. 15/745,591, granted, now 11,053,495, previously published as PCT/US2016/042498, filed on Jul. 15, 2016.
Claims priority of provisional application 62/194,003, filed on Jul. 17, 2015.
Prior Publication US 2022/0106593 A1, Apr. 7, 2022
Int. Cl. C07H 21/04 (2006.01); A61K 47/54 (2017.01); A61K 47/55 (2017.01); C07H 21/00 (2006.01); C12N 15/11 (2006.01); C12N 15/113 (2010.01)
CPC C12N 15/113 (2013.01) [A61K 47/549 (2017.08); A61K 47/55 (2017.08); C07H 21/00 (2013.01); C12N 15/111 (2013.01); C12N 2310/14 (2013.01); C12N 2310/20 (2017.05); C12N 2310/351 (2013.01); C12N 2310/3519 (2013.01); C12N 2310/51 (2013.01); C12N 2320/31 (2013.01)] 24 Claims
 
1. A multi-targeted molecule comprising a first double-stranded siRNA molecule and a second double-stranded siRNA molecule, wherein a sense or antisense strand of the first siRNA is covalently linked to a sense or antisense strand of the second siRNA via a linker, wherein at least one ligand is conjugated with the multi-targeted molecule, and wherein the linker comprises:

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where n is 1 to 12; and m is 1 to 12.