1430738-25-2Relevant academic research and scientific papers
Scale-up Synthesis of Tesirine
Tiberghien, Arnaud C.,Von Bulow, Christina,Barry, Conor,Ge, Huajun,Noti, Christian,Collet Leiris, Florence,McCormick, Marc,Howard, Philip W.,Parker, Jeremy S.
, p. 1241 - 1256 (2018/09/06)
This work describes the enabling synthesis of tesirine, a pyrrolobenzodiazepine antibody-drug conjugate drug-linker. Over the course of four synthetic campaigns, the discovery route was developed and scaled up to provide a robust manufacturing process. Early intermediates were produced on a kilogram scale and at high purity, without chromatography. Midstage reactions were optimized to minimize impurity formation. Late stage material was produced and purified using a small number of key high-pressure chromatography steps, ultimately resulting in a 169 g batch after 34 steps. At the time of writing, tesirine is the drug-linker component of eight antibody-drug conjugates in multiple clinical trials, four of them pivotal.
Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate Pyrrolobenzodiazepine Dimer Payload
Tiberghien, Arnaud C.,Levy, Jean-Noel,Masterson, Luke A.,Patel, Neki V.,Adams, Lauren R.,Corbett, Simon,Williams, David G.,Hartley, John A.,Howard, Philip W.
, p. 983 - 987 (2016/11/19)
Pyrrolobenzodiazepine dimers are an emerging class of warhead in the field of antibody-drug conjugates (ADCs). Tesirine (SG3249) was designed to combine potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity a
PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
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, (2015/04/28)
RJW/FP7067259 150 ABSTRACT A compound which is selected from A: A O OO O O O I O NH O O O O O O O O N H N H N H OO OH H O N N OO H N N B: 5 B O OO O O O Br O NH O O O O O O O O N H N H N H OO OH H O N N OO H N N; and C C O O N H N H O N H OO OO O O N O OO
PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES
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, (2015/04/28)
Conjugates of specific PBD dimers with an antibody that that binds to HER2, the antibody comprising a VH domain having the sequence according to SEQ ID NO. 1.
PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES
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, (2015/04/28)
Conjugates of specific PBD dimers with an antibody that binds to PSMA, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 3, 5, 7, 8, 9, or 10, optionally further comprising a VL domain having the sequence 5 according to any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18.
PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES
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, (2015/04/28)
Conjugates of specific PBD dimers with an antibody that that binds to CD19, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 2, 3, 4, 5 or 6, optionally further comprising a VL domain having the sequence according to any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12.
PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES
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, (2015/04/28)
Conjugates of specific PBD dimers with an antibody that binds to CD22, the antibody comprising a VH domain having the sequence according to SEQ ID NO. 1.
ANTIBODIES AND ANTIBODY-DRUG CONJUGATES
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, (2015/11/03)
This application provides antibodies and antigen binding fragments thereof which are capable of specifically binding the 5T4 cell surface antigen, antibody-drug conjugates, and antibody-imaging agent conjugates, as well as means and methods for producing and using them.
HUMANIZED ANTI-TN-MUC1 ANTIBODIES AND THEIR CONJUGATES
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, (2015/11/09)
Humanized anti-Tn-MUC1 antibodies and conjugates thereof. Conjugates comprising pyrrolobenzodiazepines (PBDs) having a labile protecting group in the form of a linker to the antibody are described.
NOVEL ANTIBODY CONJUGATES AND USES THEREOF
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, (2014/09/03)
Provided are novel antibody drug conjugates (ADCs), and methods of using such ADCs to treat proliferative disorders.
