US 12,311,029 B2
Proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of indoleamine 2,3-dioxygenase (IDO) protein
Gary E. Schiltz, Naperville, IL (US); and Derek A. Wainwright, Brookfield, IL (US)
Assigned to Northwestern University, Evanston, IL (US)
Filed by Northwestern University, Evanston, IL (US)
Filed on Oct. 23, 2023, as Appl. No. 18/492,746.
Application 18/492,746 is a division of application No. 17/305,311, filed on Jul. 2, 2021, granted, now 11,839,659.
Claims priority of provisional application 63/047,913, filed on Jul. 2, 2020.
Prior Publication US 2024/0165248 A1, May 23, 2024
Int. Cl. A61K 47/64 (2017.01); A61K 47/54 (2017.01); C07K 16/28 (2006.01)
CPC A61K 47/64 (2017.08) [A61K 47/545 (2017.08); C07K 16/2818 (2013.01)] 17 Claims
 
1. A method of treating cancer, the method comprising administering a pharmaceutical composition to a subject having the cancer,
wherein the pharmaceutical composition comprises
(a) a molecule having a formula MIDO-L-ME3, wherein MIDO is a moiety that binds to indoleamine 2,3-dioxygenase (IDO), L is a bond or a linker covalently attaching MIDO and ME3, and ME3 is a moiety that binds to an E3 ubiquitin ligase; and
(b) a suitable pharmaceutical carrier, excipient, or diluent,
wherein MIDO-L-ME3 has a formula

OG Complex Work Unit Chemistry
wherein X is O or NH, L comprises a polyethylene glycol moiety, an alkylalkyne moiety, and/or an aminoalkyl alkyne moiety, and ME3 is a moiety that binds to an E3 ubiquitin ligase selected from Von Hippel-Lindau (VHL) E3 ubiquitin ligase, cereblon (CRBN) E3 ubiquitin ligase, inhibitor of apoptosis protein (IAP) E3 ubiquitin ligase, and mouse double minute 2 homolog (MDM2) E3 ubiquitin ligase.