公开(公告)号：WO2021174113A1

公开(公告)日：2021-09-02

申请号：PCT/US2021/020074

申请日：2021-02-26

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： ANDREEV, Julian ,  PEREZ BAY, Andres ,  DALY, Christopher ,  DELFINO, Frank ,  HAN, Amy ,  NITTOLI, Thomas ,  OLSON, William ,  THURSTON, Gavin

IPC: A61P35/00 ,  C07K16/32 ,  C07K16/46 ,  A61K47/68

Abstract: Provided herein are bispecific antigen-binding molecules that bind HER2 and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably non-overlapping) epitopes of the extracellular domain of human HER2. The bispecific antigen-binding molecules cluster on the surface of HER2 IHC2+ and IHC3+ cells, and are internalized into the cellular lysosomes. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.

公开(公告)号：WO2019212965A1

公开(公告)日：2019-11-07

申请号：PCT/US2019/029640

申请日：2019-04-29

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： PEREZ BAY, Andres ,  ANDREEV, Julian ,  POTOCKY, Terra ,  DUAN, Xunbao

IPC: C07K16/28 ,  C07K16/32 ,  A61P35/00 ,  A61K47/68

Abstract: The protein known as human epidermal growth factor 2 (HER2) is expressed in breast cancer cells and its expression is correlated with aggressive tumor growth. The present invention provides novel full-length human (IgG) antibodies that bind to human HER2 (monospecific antibodies) or to APLP2 (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both HER2 and APLP2 and mediate internalization and degradation of HER2 via the APLP2 complex in the presence of HER2-expressing tumors. Described are bispecific antigen-binding molecules and ADCs comprising a first antigen-binding domain that specifically binds human APLP2, and a second antigen-binding domain that specifically binds human HER2. The described bispecific ADCs are capable of inhibiting the growth of certain tumors expressing HER2 and may be useful for the treatment of breast cancer and disorders in which targeting a therapeutic agent to HER2-expressing tumor cell is desirable and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of breast cancers, including breast cancers having a IHC2+ classification. The present invention also includes anti-HER2 antibody drug conjugates which inhibit tumor growth in vivo .