US 12,216,122 B2
Compositions and methods relating to detection, inhibition, and imaging of indoleamine 2,3-dioxygenase 1 (IDO1)
Heather Dawn Agnew, Culver City, CA (US); Bert Tsunyin Lai, Culver City, CA (US); and Anders Eliasen, Culver City, CA (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on May 20, 2020, as Appl. No. 16/879,611.
Claims priority of provisional application 62/850,533, filed on May 20, 2019.
Prior Publication US 2020/0371101 A1, Nov. 26, 2020
Int. Cl. G01N 33/573 (2006.01); C07K 1/06 (2006.01); C07K 5/08 (2006.01); C07K 5/10 (2006.01); C07K 7/06 (2006.01); C12N 9/02 (2006.01); G01N 33/68 (2006.01); G01N 33/534 (2006.01)
CPC G01N 33/573 (2013.01) [C07K 5/10 (2013.01); C07K 7/06 (2013.01); C12N 9/0069 (2013.01); G01N 33/68 (2013.01); C07K 2319/70 (2013.01); C12Q 2521/501 (2013.01); C12Y 113/11052 (2013.01); G01N 33/534 (2013.01); G01N 2333/90241 (2013.01)] 17 Claims
OG exemplary drawing
 
1. A heterobiligand comprising a first ligand having affinity for an epitope on indoleamine 2,3-dioxygenase 1 (IDO1), a linker, and a second ligand, wherein the second ligand comprises a small molecule inhibitor of IDO1, wherein the linker links the first ligand and the second ligand, wherein the heterobiligand specifically binds and inhibits IDO1, wherein IDO1 comprises an active site, and wherein the small molecule inhibitor of IDO1 binds the IDO1 active site, wherein the first ligand comprises an amino acid sequence selected from the group consisting of wyvay (SEQ ID NO:2), wyaay (SEQ ID NO: 8), (F-Phe)n(Me-Trp)(Me-Trp)w (SEQ ID NO:5), (F-Phe)rhl(Me-Trp) (SEQ ID NO: 9), (F-Phe)t(Me-Trp)y(Me-Trp) (SEQ ID NO:10), G(F-Phe)nwk (SEQ ID NO:11), (Me-Trp)ffkf (SEQ ID NO:12), ndn(Me-Trp)w (SEQ ID NO:13), npv(F-Phe)w (SEQ ID NO: 14), ntk(Me-Trp)p (SEQ ID NO:15), n(Me-Trp)p(Me-Trp)f (SEQ ID NO:16), pp(Me-Trp)s(Me-Trp) (SEQ ID NO:17), yyy(Me-Trp)t (SEQ ID NO:18), and yfn(Me-Trp)(Me-Trp) (SEQ ID NO:19); and
wherein the small molecule inhibitor of IDO1 is

OG Complex Work Unit Chemistry
wherein X is S, O, or NH, wherein R1 is —CH2—R2—, —(CH2)n—R2—, absent, —(CH2—CH2—O)m—CH2—CH2—R2—, or —CH2—CH2—NH—SO2—R2—, wherein R2 is —CO— or —NH—, wherein n is an integer from 2 to 10, wherein m is an integer from 1 to 6.