US 12,448,488 B2
Conjugate of bio-related substance and block polymer, and block polymer derivative for obtaining said conjugate
Hiroki Yoshioka, Kawasaki (JP); Midori Hirai, Kawasaki (JP); Masaki Kamiya, Kawasaki (JP); and Gianfranco Pasut, Padua (IT)
Assigned to NOF CORPORATION, Tokyo (JP); and UNIVERSITA' DEGLI STUDI DI PADOVA, Padua (IT)
Appl. No. 17/603,275
Filed by NOF CORPORATION, Tokyo (JP); and UNIVERSITA' DEGLI STUDI DI PADOVA, Padua (IT)
PCT Filed Apr. 15, 2019, PCT No. PCT/IT2019/000031
§ 371(c)(1), (2) Date Oct. 12, 2021,
PCT Pub. No. WO2020/213015, PCT Pub. Date Oct. 22, 2020.
Prior Publication US 2022/0185969 A1, Jun. 16, 2022
Int. Cl. A61K 31/765 (2006.01); A61K 31/785 (2006.01); A61K 38/27 (2006.01); A61K 47/54 (2017.01); A61K 47/56 (2017.01); A61K 47/59 (2017.01); C08G 81/00 (2006.01); C08G 81/02 (2006.01)
CPC C08G 81/028 (2013.01) [A61K 38/27 (2013.01); A61K 47/54 (2017.08); A61K 47/595 (2017.08)] 10 Claims
 
1. A conjugate of a block polymer and a bio-related substance, which is represented by the following formula (1):

OG Complex Work Unit Chemistry
wherein A is a bio-related substance selected from the group consisting of a cytokine, a hormone, an enzyme, an antibody, and a nucleic acid, L1, L2, L3 are each independently a single bond or a divalent linker, Q is a residue of a compound having 2 or 3 active hydrogens, m is 10-1400, n is 2-100, x is 1 or 2, R is a hydrogen atom or an acyl group, p is 1 or 2, and y is 1-40.
 
2. The conjugate according to claim 1, wherein, in the formula (1), y is 1.
 
8. The conjugate according to claim 1, wherein, in the formula (1), m is 40-1200 and n is 5-50.
 
9. The conjugate according to claim 1, wherein, in the formula (1), Q is a residue of a compound selected from the group consisting of ethylene glycol, glycerol, lysine, aspartic acid and glutamic acid.
 
10. The conjugate according to claim 1, wherein, in the formula (1), L1, L2, L3 are each independently selected from the group consisting of a single bond, a phenylene group, an amide bond, an ether bond, a thioether bond, a urethane bond, a secondary amino group, a carbonyl group, a urea bond, a triazine group, a maleimide group added with thiol, an oxyme bond, and an alkylene group optionally containing one or more kinds selected from the group consisting of a single bond, a phenylene group, an amide bond, an ether bond, a thioether bond, a urethane bond, a secondary amino group, a carbonyl group, a urea bond, a triazine group, a maleimide group added with thiol and an oxyme bond.