Agonists of TREM2

US12384844B2 · kind B2 · utility

Assignee

• Genentech, Inc. · US

Inventors

• Ainhoa Echeverria Larraza · South San Francisco, US
• David Verne Hansen · Mapleton, US
• Isidro Hotzel · Brisbane, US
• Yi-Chun Hsiao · San Mateo, US
• Zhonghua Lin · San Francisco, US
• Dhaya SESHASAYEE · Cupertino, US
• Benny Chih · Millbrae, US

Key dates

• Filing date: May 12, 2022
• Grant date: Aug 12, 2025
• Expiry date: Nov 23, 2043

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2317/92
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

This application discloses, inter alia, certain antibodies that specifically bind to human TREM2 (triggering receptor expressed on myeloid cells 2). In some embodiments, the antibodies act as TREM2 agonists. In some embodiments, antibodies herein specifically bind to the stalk region of intact, human TREM2, without binding to soluble TREM2, which is the product of TREM2 cleavage between residues H157 and S158. In some embodiments, the antibodies act as TREM2 agonists, specifically bind to the stalk region of TREM2 with dissociation constants ranging from 10 nM to as low as 100-500 pM, 10-50 pM, or 1-10 pM, specifically bind to a TREM2 epitope spanning the H157-S158 cleavage site, and do not bind to soluble TREM2. In some embodiments, antibodies herein also inhibit shedding of soluble TREM2 in a human microglia cell model and in vivo in a mouse model, decrease levels of soluble TREM2 in plasma, CSF and/or the brain, enhance survival of human microglia cells, and increase Aβ plaque formation and compaction in a human microglia model (for example, as measured by increased Aβ plaque intensity and/or increased X04 plaque intensity in human microglia), and thus, may provide a number of n…