公开(公告)号：US20250011450A1

公开(公告)日：2025-01-09

申请号：US18749445

申请日：2024-06-20

Applicant: Genentech, Inc.

Inventor： Gregory Alan LAZAR ,  Brandon LEONARD ,  Matthew G. ROMEI

IPC: C07K16/28 ,  C12N15/10

Abstract: Provided herein are antibodies such as human or humanized antibodies with a modified heavy chain variable (VH) domain such that the antibodies adopt a constrained conformation (e.g., an i-shaped format) upon engaging the antigen(s) the antibodies bind to, thereby confer agonistic activities. In some cases, the antibodies are full-length antibodies (e.g., IgG antibodies). In some cases, the antibodies are monovalent antibodies (e.g., Fabs). In some cases, the antibodies target receptors which require clustering for activation (e.g., TNFR superfamily receptors). In some cases, the antibodies target two antigens on a molecule that have two or more subunits (e.g., an IL-2 receptor). Also provided herein are methods of making and using such antibodies and libraries for discovering or screening such antibodies.