US 12,337,038 B2
Conjugates comprising cleavable beta-glucuronide-containing linkers
Akbar Husain Khan, Waltham, MA (US); Andreas Lothar Severino Maderna, Waltham, MA (US); Maximillian Taro William Lee, London (GB); Mattia Cocco, London (GB); Boliang Deng, Waltham, MA (US); Jonathan David Beadle, London (GB); Albano Galan Coca, London (GB); Alla Pryyma, Waltham, MA (US); Nicole Danielle Bartolo, Waltham, MA (US); Luke Masterson, London (GB); and William Robert Fraser Goundry, Macclesfield (GB)
Filed by AstraZeneca AB, Södertälje (SE)
Filed on Apr. 9, 2024, as Appl. No. 18/630,179.
Claims priority of provisional application 63/496,709, filed on Apr. 18, 2023.
Prior Publication US 2024/0366781 A1, Nov. 7, 2024
Int. Cl. A61K 47/68 (2017.01); A61K 47/54 (2017.01); A61K 47/60 (2017.01); A61P 35/00 (2006.01)
CPC A61K 47/6889 (2017.08) [A61K 47/545 (2017.08); A61K 47/549 (2017.08); A61K 47/60 (2017.08); A61K 47/6849 (2017.08); A61P 35/00 (2018.01)] 26 Claims
 
1. A conjugate of Formula (I)
Ab-(GA-JA-DR)k  (I)
or a pharmaceutically acceptable salt thereof, wherein
Ab is an antibody or antigen-binding fragment thereof,
k is an integer from 1 to 10,
each GA is independently a conjugation group conjugated to the antibody or antigen-binding fragment thereof,
each DR is independently a drug comprising a nitrogen atom NR,
each JA is independently a group of Formula (IA)

OG Complex Work Unit Chemistry
E is (CH2)n1, wherein n1 is 0, 1, 2 or 3,
Q is

OG Complex Work Unit Chemistry
R1 is C1-4 alkyl,
X is (CH2)n2, wherein n2 is 0, 1, 2 or 3,
Y is (CH2)n3, wherein n3 is 0, 1, 2, 3 or 4,
Z is (CH2)n4, wherein n4 is 1, 2, 3, 4 or 5,
m is an integer from 5 to 17,
p is 1 or 0,
(GA) indicates the point of attachment to GA, and
(NR) indicates the point of attachment to the nitrogen atom NR.