US 12,433,847 B2
Branched poly(-amino esters) for the delivery of nucleic acids
Carlo Giovanni Traverso, Newton, MA (US); Ameya R. Kirtane, Minneapolis, MN (US); Robert S. Langer, Newton, MA (US); Hyunjoon Kim, Cambridge, MA (US); Gary W Liu, Cambridge, MA (US); James Byrne, Boston, MA (US); Daniel Reker, Durham, NC (US); Yunhua Shi, Belmont, MA (US); Grace Junyue Zhong, Cambridge, MA (US); and Netra Rajesh, Brampton (CA)
Assigned to Massachusetts Institute of Technology, Cambridge, MA (US); and The Brigham and Women's Hospital, Inc., Boston, MA (US)
Filed by Massachusetts Institute of Technology, Cambridge, MA (US); and The Brigham and Women's Hospital, Inc., Boston, MA (US)
Filed on Mar. 8, 2022, as Appl. No. 17/689,314.
Claims priority of provisional application 63/158,441, filed on Mar. 9, 2021.
Prior Publication US 2022/0287983 A1, Sep. 15, 2022
Int. Cl. A61K 9/51 (2006.01); A61K 39/00 (2006.01); A61K 48/00 (2006.01); A61P 35/00 (2006.01); C08G 63/682 (2006.01); C08G 63/685 (2006.01)
CPC A61K 9/5153 (2013.01) [A61K 39/0011 (2013.01); A61K 48/0041 (2013.01); A61P 35/00 (2018.01); C08G 63/685 (2013.01); A61K 2039/53 (2013.01)] 20 Claims
 
1. A branched polymer of Formula (I):
L-(R)n  (I)
or a salt thereof, wherein:
L is a substituted or unsubstituted heteroalkylene;
n is 3, 4, 5, or 6; and
each R is independently hydrogen, Formula (II), or Formula (III);
wherein Formula (II) is:

OG Complex Work Unit Chemistry
wherein:
m is an integer of 1-1000, inclusive;
A is optionally substituted alkylene or optionally substituted heteroalkylene;
X is —CH═CH2, —CH2CH2OR2, —CH2CH2SR3, —CH2CH2N(R2)(R3), or —CH2CH2L(R4)q;
q is 2, 3, 4, or 5;
R1 is optionally substituted alkyl or optionally substituted heteroalkyl;
R2 is hydrogen, optionally substituted alkyl, or optionally substituted heteroalkyl;
R3 is optionally substituted alkyl or optionally substituted heteroalkyl; or
R2 and R3 combine to form a 4-7 membered ring; and
each R4 is independently hydrogen, Formula (II), or Formula (III);
wherein Formula (III) is:

OG Complex Work Unit Chemistry
wherein:
p is an integer of 1-1000, inclusive;
B is optionally substituted alkylene or optionally substituted heteroalkylene;
Z is —CH═CH2, —CH2CH2OR6, —CH2CH2SR7, —CH2CH2N(R6)(R7), or —CH2CH2L(R8)v;
v is 2, 3, 4, or 5;
R5 is optionally substituted alkyl or optionally substituted heteroalkyl;
R6 is hydrogen, optionally substituted alkyl, or optionally substituted heteroalkyl;
R7 is optionally substituted alkyl or optionally substituted heteroalkyl; or
R6 and R7 combine to form a 4-7 membered ring; and
each R8 is independently hydrogen, Formula (II), or Formula (III);
provided that at least one R is Formula (II) and at least one R is Formula (III), and provided that Formula (II) and Formula (III) are not the same.