US 12,303,571 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 Jul. 13, 2021, as Appl. No. 17/373,987.
Application 17/373,987 is a continuation 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 2021/0346523 A1, Nov. 11, 2021
Int. Cl. A61B 5/00 (2006.01); A61B 8/00 (2006.01); A61B 10/00 (2006.01); A61K 47/68 (2017.01); A61K 49/00 (2006.01); 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 31/194 (2006.01); A61K 45/06 (2006.01)
CPC A61K 49/0058 (2013.01) [A61K 47/68031 (2023.08); A61K 47/68033 (2023.08); A61K 47/68035 (2023.08); 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)] 13 Claims
 
1. A compound having a structure of formula (III)

OG Complex Work Unit Chemistry
wherein:
custom character represents either a single bond or a double bond;
Cb is a cell-binding agent selected from the group consisting of an antibody, a protein and a peptide;
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 of alkyl; C2-C8 of heteroalkyl, alkylcycloalkyl, or heterocycloalkyl; C3-C8 of aryl, Ar-alkyl, heterocyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, or heteroaryl; 1-8 amino acids; wherein R3 and R3, are independently H; C1-C8 of alkyl; C2-C8 of heteroalkyl, alkylcycloalkyl, or heterocycloalkyl; C3-C8 of aryl, Ar-alkyl, heterocyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, or heteroaryl; C1-C8 of esters, 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;
R1 and R2 are independently one or more, or repeating, or a combining thereof, of the following components:

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
natural or unnatural peptides containing 1-20 amino acids;
m1 and m2 are independently an integer from 1 to 30;
n is an integer from 1 to 30; and
Z1 is a function group that enables the compound to react with a cytotoxic drug, to form a disulfide, thioether, thioester, peptide, hydrazone, ether, ester, carbamate, carbonate, secondary, tertiary, or quarter amine, imine, cycloheteroalkyl, heteroaromatic, alkoxime or amide bond.