MODULATING ANTIBODY EFFECTOR FUNCTIONS

• Main Authors: PADAKI Rupa, BRETZLAFF William S, KUHNS Scott Thomas, ZHANG Qingchun
• Format: Patent
• Language: English; Spanish
• Published: 07.03.2022
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

Provided herein are methods of modulating Fc gamma Receptor (FcγR)-mediated cytotoxicity of an antibody composition. In exemplary embodiments, the method comprises (1) increasing or decreasing the amount of terminal β-galactose at the N-297 glycosylation site of panitumumab, or increasing or decreasing the amount of panitumumab molecules that comprise G1, G1a, G1b and/or G2 galactosylated glycan at the N-297 site, (2) increasing or decreasing the amount of panitumumab molecules that comprise fucosylated glycan at the N-297 site, or increasing or decreasing the amount of panitumumab molecules that comprise afucosylated glycan at the N-297 site, and (3) increasing or decreasing the amount of panitumumab molecules that comprise a high-mannose glycan at the N-297 site. En el presente documento se proporcionan métodos para modular la citotoxicidad mediada por el receptor Fc gamma (FcyR) de una composición anticuerpo. En realizaciones ilustrativas, el método comprende (1) aumentar o disminuir la cantidad B-galactosa terminal en el sitio de glucosilación N-297 de panitumumab, o aumentar o disminuir la cantidad de moléculas de panitumumab que comprenden glucano galactosilado G1, G1a, G1b y/o G2 en el sitio N-297, (2) aumentar o disminuir la cantidad de moléculas de panitumumab que comprenden glucano fucosilado en el sitio N-297, o aumentar o disminuir la cantidad de moléculas de panitumumab que comprenden glucano afucosilado en el sitio N-297 y (3) aumentar o disminuir la cantidad de moléculas de panitumumab que comprenden un glucano con alto contenido de manosa en el sitio N-297.