31-05-2018 дата публикации
Номер: US20180147295A1
Принадлежит:
A type of trimaleimide linkers and uses thereof are disclosed. The trimaleimide linkers can be applied for preparation of antibody-drug conjugate as shown by formula I: L-(T-A-D)I wherein, L is an antibody, antibody fragment or protein; T is a trimaleimide linker; A is a cleavable linker group or a noncleavable linker; D is a drug; n is an integer ranging from 1 to 8. 2. The antibody-drug conjugate of claim 1 , wherein A is a cleavable linker group or a noncleavable linker.5. The antibody-drug conjugate of claim 1 , wherein the antibody targets cell surface receptors or tumor-related antigens.6. The antibody-drug conjugate of claim 1 , wherein the drug is cytotoxic drug claim 1 , anti-autoimmune disease drug claim 1 , or anti-inflammation drug. The invention relates to pharmaceutical treatment of tumors or other diseases via antibody-drug conjugates (ADCs). The invention further relates to preparation of ADCs utilizing a specific trimaleimide linker to control the drug/antibody ratio (DAR).Antibody-drug conjugates are a kind of novel targeted therapeutic agents for the treatment of cancer and auto-immune diseases. The basic design philosophy originated from the notions of “magic bullet” and “drug targeting”, i.e. delivering drugs to the target region via specific carriers, which was firstly proposed by Paul Ehrlich in 1931. However, restricted by the technologies of antibody and high potency cytotoxic drug, the first ADC drug, Malotarg™ (for the treatment of acute myleocytic leukemia, AML), was not approved by FDA until 2000. Recently, FDA approved two ADC drugs, Adcetris™ (for the treatment of HL/ALCL by Seattle Genetics, 2011) and Kadcyla™ (for the treatment of breast cancer by Genentech, 2013), indicating that the rapid development stage of ADCs for cancer treatment is coming. In traditional ADC structures, highly-potent cytotoxic drugs are normally linked, via different linkers, to the ε-amino group of lysine residues or cysteine residues (after full/partial ...
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