Design and synthesis of enzyme inhibitors as potential antibacterials and antimalarials

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Antibody-Oligonucleotide Conjugates: A Twist to Antibody-Drug Conjugates

A summary of the key technological advancements in the preparation of antibody–oligonucleotide conjugates (AOCs) and the distinct advantages and disadvantages of AOCs as novel therapeutics are presented. The merits and demerits of the different approaches to conjugating oligonucleotides to antibodies, antibody fragments or other proteins, mainly from the perspective of AOC purification and analytical characterizations, are assessed. The lessons learned from in vitro and in vivo studies, especially the findings related to silencing, trafficking, and cytotoxicity of the conjugates, are also summarized

Development of a Single-Step Antibody–Drug Conjugate Purification Process with Membrane Chromatography

Membrane chromatography is routinely used to remove host cell proteins, viral particles, and aggregates during antibody downstream processing. The application of membrane chromatography to the field of antibody-drug conjugates (ADCs) has been applied in a limited capacity and in only specialized scenarios. Here, we utilized the characteristics of the membrane adsorbers, Sartobind® S and Phenyl, for aggregate and payload clearance while polishing the ADC in a single chromatographic run. The Sartobind® S membrane was used in the removal of excess payload, while the Sartobind® Phenyl was used to polish the ADC by clearance of unwanted drug-to-antibody ratio (DAR) species and aggregates. The Sartobind® S membrane reproducibly achieved log-fold clearance of free payload with a 10 membrane-volume wash. Application of the Sartobind® Phenyl decreased aggregates and higher DAR species while increasing DAR homogeneity. The Sartobind® S and Phenyl membranes were placed in tandem to simplify the process in a single chromatographic run. With the optimized binding, washing, and elution conditions, the tandem membrane approach was performed in a shorter timescale with minimum solvent consumption and high yield. The application of the tandem membrane chromatography system presents a novel and efficient purification scheme that can be realized during ADC manufacturing