US 12,397,069 B2
Fibroblast activation protein (FAP)-targeted imaging and therapy
Philip Stewart Low, West Lafayette, IN (US); and Jyoti Roy, West Lafayette, IN (US)
Assigned to PURDUE RESEARCH FOUNDATION, West Lafayette, IN (US)
Filed by PURDUE RESEARCH FOUNDATION, West Lafayette, IN (US)
Filed on Dec. 16, 2021, as Appl. No. 17/553,113.
Application 17/553,113 is a continuation of application No. 17/245,872, filed on Apr. 30, 2021, granted, now 11,872,291.
Application 17/245,872 is a continuation of application No. 16/469,907, abandoned, previously published as PCT/US2017/065995, filed on Dec. 13, 2017.
Claims priority of provisional application 62/434,380, filed on Dec. 14, 2016.
Claims priority of provisional application 62/575,050, filed on Oct. 20, 2017.
Prior Publication US 2022/0105208 A1, Apr. 7, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 51/04 (2006.01); A61K 47/55 (2017.01); A61K 49/00 (2006.01); G01N 33/569 (2006.01)
CPC A61K 51/0497 (2013.01) [A61K 47/55 (2017.08); A61K 49/0032 (2013.01); A61K 49/0043 (2013.01); A61K 49/0052 (2013.01); G01N 33/56966 (2013.01)] 22 Claims
 
1. A conjugate, or a pharmaceutically acceptable salt thereof, having a structure
B-L-X,
wherein B is a fibroblast activation protein (FAP) inhibitor; is of the formula:

OG Complex Work Unit Chemistry
wherein each of R1 and R2 is independently selected from the group consisting of hydrogen, halogen, and C1-C4 alkyl; R3 is a C1-C4 alkyl, nitrile, or isonitrile;
and each of R4, R5, and R6 is independently selected from the group consisting of hydrogen, halogen, and C1-C4 alkyl; and n is an integer from 1 to 8
L is a bivalent linker comprising at least one amino acid selected from the group consisting of Glu and Cys, or a derivative thereof; and
X comprises a near infrared (NIR) dye, a radioactive imaging agent, or a therapeutic agent effective against cancer cells and/or cancer-associated fibroblasts (CAF),
wherein the linker further comprises a fragment of the formula

OG Complex Work Unit Chemistry
wherein
m is an integer from 0 to 9;
p is an integer from 3 to 10; and
q is an integer from 3 to 100.