US 11,730,817 B2
Pro-cyclic dinucleotides and pro-cyclic dinucleotide conjugates for cytokine induction
Thierry Lioux, Balma (FR); Fabienne Vernejoul, Toulouse (FR); Cédric Boularan, Toulouse (FR); and Michèle Tiraby, Toulouse (FR)
Assigned to INVIVOGEN, Toulouse (FR)
Appl. No. 16/958,463
Filed by INVIVOGEN, Toulouse (FR)
PCT Filed Dec. 28, 2018, PCT No. PCT/EP2018/097128
§ 371(c)(1), (2) Date Jun. 26, 2020,
PCT Pub. No. WO2019/129880, PCT Pub. Date Jul. 4, 2019.
Claims priority of application No. 17306981 (EP), filed on Dec. 29, 2017.
Prior Publication US 2021/0353760 A1, Nov. 18, 2021
Prior Publication US 2022/0339287 A9, Oct. 27, 2022
Prior Publication US 2023/0116913 A2, Apr. 13, 2023
Int. Cl. A61K 47/54 (2017.01); A61K 47/68 (2017.01); A61K 47/64 (2017.01); A61K 47/65 (2017.01); A61K 31/7084 (2006.01); A61K 45/06 (2006.01)
CPC A61K 47/549 (2017.08) [A61K 31/7084 (2013.01); A61K 45/06 (2013.01); A61K 47/643 (2017.08); A61K 47/65 (2017.08); A61K 47/6807 (2017.08); A61K 47/6849 (2017.08); A61K 47/6889 (2017.08)] 25 Claims
OG exemplary drawing
 
1. A Pro-CDN compound of Formula (Ib):

OG Complex Work Unit Chemistry
or pharmaceutically acceptable salts, stereoisomers, tautomers or solvates thereof;
wherein:
the CDN unit is a cyclic dinucleotide monophosphorothioate or diphosphorothioate of Formula (IIa):

OG Complex Work Unit Chemistry
wherein:
X1 and Y1 are independently H or F;
X2 and Y2 are independently H or F;
Z1 is O or S;
R1 is H when Z1 is O;
R1 is H or a linker system when Z1 is S;
B1 and B2 are purine bases chosen from:

OG Complex Work Unit Chemistry
the specifier is a peptide sequence which can be cleaved by a specific protease; and
W1 is an amide, an ester, a urea, a disulfide bridge, a carbamate, a hydrazone, an imine, an oxime, or a triazole group.