发明名称 |
ANTIBODY-DRUG CONJUGATES WITH HIGH DRUG LOADING |
摘要 |
The present invention provides transglutaminase-mediated antibody-drug conjugates with high anti-body-drug ratio (DAR) comprising 1) glutamine-containing tags, endogenous glutamines, and/or endogenous glutamines made reactive by antibody engineering or an engineered transglutaminase (e.g., with altered substrate specifity); and 2) amine donor agents comprising amine donor units, linkers, and agent moieties, wherein the DAR is at least about 5. The invention also provides methods of making and methods of using such higher drug loaded antibody-drug conjugates. |
申请公布号 |
US2017043033(A1) |
申请公布日期 |
2017.02.16 |
申请号 |
US201515306481 |
申请日期 |
2015.04.21 |
申请人 |
Rinat Neuroscience Corp. ;Pfizer Inc. |
发明人 |
STROP Pavel;DELARIA Katherine Anne;DORYWALSKA Magdalena;FOLETTI Davide Luciano;DUSHIN Russell George;SHELTON David Louis;RAJPAL Arvind |
分类号 |
A61K47/48;G01N33/574;C07K16/30;A61K31/427 |
主分类号 |
A61K47/48 |
代理机构 |
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代理人 |
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主权项 |
1. An antibody-drug conjugate comprising the formula: antibody-(T-(X-Y-Za)b)c, wherein:
T is 1) a glutamine-containing tag engineered at a specific site, 2) an endogenous glutamine, and/or 3) an endogenous glutamine made reactive by antibody engineering or an engineered transglutaminase; X is an amine donor unit; Y is a linker; and Z is an agent moiety; X-Y-Z is an amine donor agent site-specifically conjugated to the glutamine-containing tag, the endogenous glutamine, and/or the reactive endogenous glutamine; a is an integer from 1 to 6; b is an integer from 1 to 6; c is an integer from 1 to 20; and wherein the product (drug-antibody ratio) of a, b, and c is at least about 5. |
地址 |
South San Francisco CA US |