Back to results
US 10,696,700 B2Granted
Charged linkers and their uses for conjugation
AssigneeHangzhou Dac Biotech Co., Ltd.
InventorsRobert Yongxin Zhao, Xing Li, Yuangyuang Huang, Qingliang Yang
Life of this patent
Estimating the term…
Abstract
Cell binding agent-drug conjugates comprising phosphinate-based charged linkers and methods of using such linkers and conjugates are provided.
Claims19
A compound of formula (III):
- wherein Cb represents a cell-binding agent which is an antibody, or a fragment thereof;
- n is an integer from 1 to 20;
- and
- the compound of formula (III) is formed by reacting a functional group on the cell-binding agent with Y in a compound of formula (I):
- wherein Z is a thiol, disulfide, unsubstituted or substituted pyridyldisulfide, unsubstituted or substituted amino, —ONH2, carboxy, aldehyde, ketone, azide, unsubstituted or substituted maleimido, haloacetyl, halogen, hydrazine, hydrazide or hydroxy group;
- M is H, Na, K, N+R1R2R3 or a pharmaceutical salt thereof;
- R1 and R2 are the same or different and are a linear alkyl having from 1-6 carbon atoms, branched or cyclic alkyl having from 3 to 6 carbon atoms, linear, branched or cyclic alkenyl or alkynyl having from 2 to 6 carbon atoms, polyethyleneoxy unit of formula (OCH2CH2)p, wherein p is an integer from 1 to about 1000, or a combination thereof;
- R3 is absent, a linear alkyl having from 1 to 6 carbon atoms, branched or cyclic alkyl having from 3 to 6 carbon atoms, a linear, branched or cyclic alkenyl or alkynyl having from 2 to 6 carbon atoms, polyethyleneoxy unit of formula (OCH2CH2)p, wherein p is an integer from 1 to about 1000, or a combination thereof;
- or R1, R2 and R3 are respectively a chain of atoms selected from the group consisting of C, N, O, S, Si, and P, and R1, R2 and R3 optionally covalently connect among each other;
- R4, and R5, are the same or different and are absent, H, a linear alkyl having from 1 to 6 carbon atoms, branched or cyclic alkyl having from 3 to 6 carbon atoms, linear, branched or cyclic alkenyl or alkynyl having from 2 to 6 carbon atoms, polyethyleneoxy unit of formula (OCH2CH2)p-1OCH2CH3, wherein p-1 is an integer from 1 to about 1000, or a combination thereof;
- and
- Y is an unsubstituted or substituted N-hydroxysuccinimide ester, hydrazide, p-nitrophenyl ester, dinitrophenyl ester, pentafluorophenyl ester, pyridyldisulfide, nitropyridyldisulfide, unsubstituted or substituted maleimido, β-maleimidopropionamido, haloacetate, or carboxylic acid halide.
9 more elements
Dependencies are inferred from the claim text.