Novartis Ag

Martin Allan

Qi-Ying Hu

Julien Papillon

Hidetomo Imase

Sylvie Chamoin

Liansheng Su

Lihua Yang

Lara Czabaniuk

Chung-Yeh Wu

Daniel Smith

Ping Zhang

Xilin Zhou

Troy Smith

Thomas Caya

Ming Qian

Matthew Carson

Chun Zhang

The invention provides methods to prepare protein conjugates from proteins having at least four accessible cysteine residues. In one embodiment, an antibody with four reducible disulfide linkages is reduced to provide four pairs of free cysteines. Each pair of free cysteines is reacted with a 1,3-dihaloacetone or similar reactant, linking the sulfur atoms of each pair together though a 3-carbon tether with a reactive ketone. A pair of these reactive ketones are linked together with and used to attach a single payload molecule, thus conjugating the antibody to two payload groups. This method gives a stabilized antibody conjugate with high selectivity for a ratio of two payloads per antibody.

Methods for making conjugates from disulfide-containing proteins

The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R, R, R, R, Rand n are defined herein. The invention also relates to a method for manufacturing compounds of the invention, and their therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition. 

Aryl-pyridine derivatives as aldosterone synthase inhibitors

Growing community of inventors

Cambridge, MA, United States of America

Martin Allan