US 12,268,739 B2
Use of toll-like receptor 2 (TLR-2) agonist for modulating human immune response
David J. Dowling, Brighton, MA (US); Ofer Levy, Cambridge, MA (US); Francesco Borriello, Jamaica Plain, MA (US); David A. Scott, Newton, MA (US); and Spencer E. Brightman, San Diego, CA (US)
Assigned to Children's Medical Center Corporation, Boston, MA (US); and Dana-Farber Cancer Institute, Inc., Boston, MA (US)
Appl. No. 17/263,515
Filed by Children's Medical Center Corporation, Boston, MA (US); and Dana-Farber Cancer Institute, Inc., Boston, MA (US)
PCT Filed Jul. 26, 2019, PCT No. PCT/US2019/043656
§ 371(c)(1), (2) Date Jan. 26, 2021,
PCT Pub. No. WO2020/023872, PCT Pub. Date Jan. 30, 2020.
Claims priority of provisional application 62/711,450, filed on Jul. 27, 2018.
Prior Publication US 2021/0236632 A1, Aug. 5, 2021
Prior Publication US 2022/0118085 A9, Apr. 21, 2022
Prior Publication US 2023/0132397 A9, Apr. 27, 2023
Int. Cl. A61K 39/39 (2006.01); A61K 31/381 (2006.01); A61K 31/4025 (2006.01); A61K 31/438 (2006.01); A61K 31/4535 (2006.01); A61K 31/496 (2006.01); A61K 31/739 (2006.01); A61K 39/00 (2006.01); A61K 45/06 (2006.01); A61P 37/04 (2006.01); A61K 31/18 (2006.01); A61K 31/4164 (2006.01)
CPC A61K 39/39 (2013.01) [A61K 31/381 (2013.01); A61K 31/4025 (2013.01); A61K 31/438 (2013.01); A61K 31/4535 (2013.01); A61K 31/496 (2013.01); A61K 31/739 (2013.01); A61K 45/06 (2013.01); A61P 37/04 (2018.01); A61K 31/18 (2013.01); A61K 31/4164 (2013.01); A61K 2039/55505 (2013.01); A61K 2039/55511 (2013.01); A61K 2039/55555 (2013.01); A61K 2039/55566 (2013.01); A61K 2039/55572 (2013.01); A61K 2039/572 (2013.01); A61K 2039/575 (2013.01); C12N 2760/16134 (2013.01); C12N 2760/16234 (2013.01)] 18 Claims
 
1. A composition comprising an antigen and a Toll-like receptor 2 (TLR2) agonist, wherein the TLR2 agonist is a compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen or optionally substituted alkyl;
R2 is hydrogen or optionally substituted alkyl; or R1 and R2 are joined together with the intervening atoms to form a substituted or unsubstituted carbocyclic ring, substituted or unsubstituted heterocyclic ring, or substituted or unsubstituted heteroaryl ring;
R3 is hydrogen, halogen, optionally substituted alkyl, —ORa1, or —N(Ra2)2, wherein Ra1 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group when attached to an oxygen atom;
wherein each occurrence of Ra2 is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;
R is hydrogen or optionally substituted alkyl;
X is O or S; and
R4 is hydrogen, optionally substituted heterocyclyl, or optionally substituted aryl.