	US 12,343,398 B2
	Biodegradable lipids for the delivery of active agents
Martin Maier, Cambridge, MA (US); Muthusamy Jayaraman, Cambridge, MA (US); Akin Akinc, Cambridge, MA (US); Shigeo Matsuda, Cambridge, MA (US); Pachamuthu Kandasamy, Cambridge, MA (US); Kallanthottathil G. Rajeev, Cambridge, MA (US); Muthiah Manoharan, Cambridge, MA (US); Jayaprakash K. Nair, Cambridge, MA (US); and Thomas A. Baillie, Cambridge, MA (US)
Assigned to ALNYLAM PHARMACEUTICALS, INC., Cambridge, MA (US)
Filed by ALNYLAM PHARMACEUTICALS, INC., Cambridge, MA (US)
Filed on Mar. 4, 2024, as Appl. No. 18/594,172.
Application 18/594,172 is a continuation of application No. 18/304,097, filed on Apr. 20, 2023.
Application 18/304,097 is a continuation of application No. 17/644,914, filed on Dec. 17, 2021, granted, now 11,679,158, issued on Jun. 20, 2023.
Application 17/644,914 is a continuation of application No. 17/302,311, filed on Apr. 29, 2021, granted, now 11,246,933, issued on Feb. 15, 2022.
Application 17/302,311 is a continuation of application No. 16/520,183, filed on Jul. 23, 2019, granted, now 11,071,784, issued on Jul. 27, 2021.
Application 16/520,183 is a continuation of application No. 14/677,801, filed on Apr. 2, 2015, granted, now 10,369,226, issued on Aug. 6, 2019.
Application 14/677,801 is a continuation of application No. 13/708,383, filed on Dec. 7, 2012, granted, now 9,061,063, issued on Jun. 23, 2015.
Claims priority of provisional application 61/623,274, filed on Apr. 12, 2012.
Claims priority of provisional application 61/568,133, filed on Dec. 7, 2011.
Prior Publication US 2024/0285768 A1, Aug. 29, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/18 (2017.01); A61K 9/127 (2006.01); A61K 9/1272 (2025.01); A61K 9/51 (2006.01); A61K 31/7088 (2006.01); A61K 31/7105 (2006.01); A61K 31/713 (2006.01); C07C 31/125 (2006.01); C07C 211/09 (2006.01); C07C 211/10 (2006.01); C07C 211/11 (2006.01); C07C 217/08 (2006.01); C07C 229/12 (2006.01); C07C 235/06 (2006.01); C07C 251/38 (2006.01); C07C 323/12 (2006.01); C07C 323/58 (2006.01); C07C 327/22 (2006.01); C07C 327/28 (2006.01); C07C 327/32 (2006.01); C07D 207/32 (2006.01); C07D 233/54 (2006.01); C07D 295/08 (2006.01); C07D 295/12 (2006.01); C07D 295/14 (2006.01); C07D 317/30 (2006.01); C07F 5/02 (2006.01)

CPC A61K 47/18 (2013.01) [A61K 9/1272 (2013.01); A61K 9/5123 (2013.01); A61K 31/7088 (2013.01); A61K 31/7105 (2013.01); A61K 31/713 (2013.01); C07C 31/125 (2013.01); C07C 211/09 (2013.01); C07C 211/10 (2013.01); C07C 211/11 (2013.01); C07C 217/08 (2013.01); C07C 229/12 (2013.01); C07C 235/06 (2013.01); C07C 251/38 (2013.01); C07C 323/12 (2013.01); C07C 323/58 (2013.01); C07C 327/22 (2013.01); C07C 327/28 (2013.01); C07C 327/32 (2013.01); C07D 207/32 (2013.01); C07D 233/54 (2013.01); C07D 295/08 (2013.01); C07D 295/12 (2013.01); C07D 295/14 (2013.01); C07D 317/30 (2013.01); C07F 5/022 (2013.01)]

30 Claims

1. In a lipid having a protonable primary group and two hydrophobic tails directly bonded to the primary group, the improvement comprising

each of the two hydrophobic tails having the formula -(hydrophobic chain)-(C(O)O)—(hydrophobic chain), wherein each hydrophobic chain consists of an aliphatic chain; and

each of the two hydrophobic tails having a total carbon atom content of from 17 to 26 carbon atoms, wherein

at least one hydrophobic tail is of the formula:

wherein R¹³is a C₁₃-C₁₇alkyl, wherein

the maximum length of R¹³from its attachment point to the ester group is 11 carbon atoms, and

R¹³comprises (i) a carbon atom that is directly bonded to the ester, (ii) two alkyl groups directly bonded to the carbon atom that is bonded to the ester, and (iii) a hydrogen atom directly bonded to the carbon atom that is bonded to the ester.