US 11,779,663 B2
Specific conjugation linkers, specific immunoconjugates thereof, methods of making and uses such conjugates thereof
Robert Yongxin Zhao, Lexington, MA (US); Qingliang Yang, Hangzhou (CN); Yuanyuan Huang, Hangzhou (CN); Shun Gai, Hangzhou (CN); Linyao Zhao, Hangzhou (CN); Hangbo Ye, Hangzhou (CN); Huihui Guo, Hangzhou (CN); Qianqian Tong, Hangzhou (CN); Minjun Cao, Hangzhou (CN); Junxiang Jia, Hangzhou (CN); Chengyu Yang, Hangzhou (CN); Wenjun Li, Hangzhou (CN); Xiaomai Zhou, Hangzhou (CN); Hongsheng Xie, Hangzhou (CN); Chen Lin, Hangzhou (CN); Zhixiang Guo, Hangzhou (CN); and Zhicang Ye, Hangzhou (CN)
Assigned to HANGZHOU DAC BIOTECH CO., LTD., Hangzhou (CN)
Filed by Hangzhou DAC Biotech Co., Ltd., Hangzhou (CN); and Robert Yongxin Zhao, Lexington, MA (US)
Filed on Nov. 9, 2020, as Appl. No. 17/93,184.
Application 17/093,184 is a division of application No. 16/074,981, granted, now 11,129,910, previously published as PCT/IB2016/050580, filed on Feb. 4, 2016.
Prior Publication US 2021/0052747 A1, Feb. 25, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61B 5/00 (2006.01); A61B 8/00 (2006.01); A61B 10/00 (2006.01); A61K 49/00 (2006.01); A61K 47/68 (2017.01); C07D 417/12 (2006.01); C07D 417/14 (2006.01); C07D 498/18 (2006.01); C07D 513/22 (2006.01); C07D 519/00 (2006.01); A61K 45/06 (2006.01); A61K 31/194 (2006.01)
CPC A61K 49/0058 (2013.01) [A61K 47/6809 (2017.08); A61K 47/6829 (2017.08); A61K 47/6889 (2017.08); A61K 49/0032 (2013.01); A61K 49/0043 (2013.01); C07D 417/12 (2013.01); C07D 417/14 (2013.01); C07D 498/18 (2013.01); C07D 513/22 (2013.01); C07D 519/00 (2013.01); A61K 31/194 (2013.01); A61K 45/06 (2013.01)] 10 Claims
 
1. A bridge linker compound of Formula (I)

OG Complex Work Unit Chemistry
wherein:
“custom character” represents a triple bond;
provided that the component:

OG Complex Work Unit Chemistry
which is acetylenedicarboxyl group;
R1 is selected from the group consisting of C1-C8 alkyl; C2-C8 heteroalkyl, alkylcycloalkyl, or heterocycloalkyl; C3-C8 aryl, Ar-alkyl, heterocyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, or heteroaryl; C1-C8 ester, ether, or amide; polyethyleneoxy unit of formula (OCH2CH2)p or (OCH2CH(CH3))p, wherein p is an integer from 0 to about 1000, and a combination thereof,
or R1 is a chain of atoms selected from the group consisting of C, N, O, S, Si, and P, which covalently connects to X1 and Z1;
X1 and X2 are independently absent or selected from the group consisting of NH; NHNH; N(R3); N(R3)N(R3′); O; S; B(R3); Si(R3)N(R3′); P(O)(R3); C1-C8 alkyl; C2-C8 heteroalkyl, alkylcycloalkyl, or heterocycloalkyl; C3-C8 aryl, Ar-alkyl, heterocyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, or heteroaryl; 1-8 amino acids; wherein R3 and R3′ are independently H; C1-C8 alkyl; C2-C8 heteroalkyl, alkylcycloalkyl, or heterocycloalkyl; C3-C8 aryl, Ar-alkyl, heterocyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, or heteroaryl; C1-C8 ester, ether, or amide; polyethyleneoxy unit of formula (OCH2CH2)p or (OCH2CH(CH3))p, wherein p is an integer from 0 to about 1000, and a combination thereof,
R2 is independently selected from the group consisting of OH, H, NH2; SH; NHNH2; N(R3)(R3′); N(R3)NH(R3′); polyethyleneoxy unit of formula (OCH2CH2)pOR3, (OCH2CH(CH3))pOR3, NH(CH2CH2O)pR3, NH(CH2CH(CH3)O)pR3, N[(CH2CH2O)pR3][(CH2CH2O)p′R3′], (OCH2CH2)pCOOR3, or CH2CH2(OCH2CH2)pCOOR3, wherein p and p′ are independently an integer selected from 0 to about 1000, or a combination thereof; C1-C8 alkyl; C2-C8 heteroalkyl, alkylcycloalkyl, or heterocycloalkyl; and C3-C8 aryl, Ar-alkyl, heterocyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, or heteroaryl; wherein R3 and R3′ are independently H; C1-C8 alkyl; C2-C8 heteroalkyl, alkylcycloalkyl, or heterocycloalkyl; C3-C8 aryl, Ar-alkyl, heterocyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, or heteroaryl; C1-C8 ester, ether, or amide; 1-8 amino acids; polyethyleneoxy unit of formula (OCH2CH2)p or (OCH2CH(CH3))p, wherein p is an integer from 0 to about 1000, or a combination thereof,
m1 and m2 are independently an integer from 1 to 30;
Z1 is at least one of thiol, disulfide, amino, carboxyl, aldehyde, ketone, maleimido, haloacetyl, hydrazines, alkoxyamino, hydroxy, N-hydroxysuccinimide ester, p-nitrophenyl ester, dinitrophenyl ester, pentafluorophenyl ester, carboxylic acid chloride, carboxylic acid anhydride, pyridyldisulfide, nitropyridyldisulfide, maleimide, haloacetate, methylsulfonephenyloxadiazole, acyloxylamine, hydrazide, or alkyne.