US 12,311,030 B2
Antibody-sting agonist conjugates and their use in immunotherapy
Zhijian Chen, Dallas, TX (US); Heping Shi, Coppell, TX (US); Qi Wei, Dallas, TX (US); Chuo Chen, Dallas, TX (US); Lijun Sun, Dallas, TX (US); Jian Qiu, Dallas, TX (US); and Youtong Wu, Dallas, TX (US)
Assigned to ImmuneSensor Therapeutics, Inc., Dallas, TX (US); and The Board of Regents of the University of Texas System, Austin, TX (US)
Filed by ImmuneSensor Therapeutics, Inc., Dallas, TX (US); and The Board of Regents of the University of Texas System, Austin, TX (US)
Filed on Dec. 16, 2021, as Appl. No. 17/553,624.
Application 17/553,624 is a continuation of application No. 17/317,864, filed on May 11, 2021, granted, now 11,213,592.
Application 17/317,864 is a continuation of application No. 16/933,845, filed on Jul. 20, 2020, granted, now 11,033,635, issued on Jun. 15, 2021.
Claims priority of provisional application 62/876,590, filed on Jul. 19, 2019.
Claims priority of provisional application 63/019,212, filed on May 1, 2020.
Prior Publication US 2022/0105198 A1, Apr. 7, 2022
Int. Cl. A61P 35/00 (2006.01); A61K 47/68 (2017.01)
CPC A61K 47/6807 (2017.08) [A61K 47/6849 (2017.08); A61K 47/6851 (2017.08); A61P 35/00 (2018.01)] 17 Claims
 
1. An antibody-drug conjugate (ADC) having the structure of Formula Ia:
Ab-[-L-D]n  (Formula Ia)
wherein:
“D” represents a cyclic di-nucleotide (CDN) having the structure of Formula Ilk:

OG Complex Work Unit Chemistry
wherein
W, X, Y, and Z are independently CH or N;
R1 is C2-4alkyl substituted with a thiol group;
RP is, independently for each occurrence, hydroxyl, thiol, C1-6alkyl, —BH3−, or —NR′R″, wherein R′ and R″ are, independently for each occurrence, hydrogen or C1-6alkyl optionally substituted with one or more groups selected from halogen, thiol, hydroxyl, carboxyl, C1-6alkoxy, C1-6 hydroxyalkoxy, —OC(O)C1-6alkyl, —N(H)C(O)C1-6alkyl, —N(C1-3 alkyl)C(O)C1-6alkyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, oxo, and azido; or R′ and R″ on the same nitrogen together form a C3-5heterocyclic ring;
or a pharmaceutically acceptable salt thereof,
“Ab” represents an antibody or binding fragment thereof which binds a target antigen;
“L” represents, independently for each occurrence, a linker linking one or more Occurrences of D to Ab;
“n” represents the number of occurrences of D linked to Ab via the linker (L);
wherein the CDN (D) is covalently bound to linker (L) at the thiol group at the R1 position of the CDN.