Novel Hydrophilic Linkers and Ligand-Drug Conjugates Thereof

• Main Authors: ZHAO, Robert Yongxin, LI, Wenjun, ZHUO, Xiaotao, GAI, Shun, SUN, Sanxing, HUANG, Yuanyuan, JIA, Junxiang, LI, Xing, YANG, Qingliang, ZHOU, Xiaomai, GUO, Huihui, LIN, Chen, QU, Lan, XIE, Hongsheng, YE, Hangbo
• Format: Patent
• Language: English
• Published: 21.05.2020
• Subjects: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention provides hydrophilic linkers that are useful for linking drugs to cell-binding ligands in ligand-drug conjugates, such as antibody-drug conjugates. The 5 ligand- drug conjugate comprises a cell -binding ligand capable of binding to a particular cell population, and a drug connected to the ligand by a hydrophilic linker. The hydrophilic linker comprises one or more hydrophilic groups that render the linker hydrophilic. The hydrophilic linker may also comprise functional groups at the two termini for coupling to the drug and the cell-binding ligand respectively. WO 2016/147031 PCT/IB2015/052011 1200 - -0- PBS -U- T-DM1 E oDX-111 E *- DX-112 a) 0 5 10 15 20 25 30 35 40 Days after Initiation of Treatment Figure 1