Regeneron Pharmaceuticals, Inc.

Chia-Yang Lin

Eric L Smith

Tong Zhang

Andrew J Murphy

Samuel H Davis

Erica Pyles

Lauric Haber

Supriya Patel

Nina Liu

Michael Rosconi

Thomas Craig Meagher

Maria Del Pilar Molina-Portela

Jiaxi Wu

Jennifer A Finney

Ryan McKay

George D Yancopoulos

Dimitris Skokos

Yang Shen

Christos Kyratsous

Eric B Smith

Ann-Hwee Lee

Yan Yang

Kara Olson

Olga Sineshchekova

According to certain embodiments, the present disclosure provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds a target antigen and a second antigen binding domain that binds a complement component. In certain embodiments, the bispecific antigen-binding molecules of the present disclosure are capable of binding to the target antigen with an ECof about 10 nM or less, and/or are capable of promoting complement deposition on the target antigen with an ECof about 10 nM. In certain embodiments, the bispecific antigen-binding molecules of the disclosure are useful for treating diseases in which inhibition or reduction of the growth of an infectious agent or cancer cell is desired and/or therapeutically beneficial.

Compositions and methods for using bispecific antibodies to bind complement and a target antigen

The present invention provides multispecific antibodies that bind to EGFR and CD28 (EGFR×CD28) as well as anti-EGFR antibodies. Such antibodies may be combined with a further therapeutic agent such as an anti-PD1 antibody. Methods for treating cancers (e.g., EGFR-expressing cancer) by administering the antibodies (e.g., and combinations thereof with anti-PD1) are also provided. The EGFR×CD28 antibodies of the present invention embody a tumor-targeted immunotherapeutic modality combined with PD-1 inhibition. These bispecific antibodies bind a tumor-specific antigen (TSA) (EGFR) with one arm and the co-stimulatory receptor, CD28, on T-cells with the other arm. Combination therapy with PD-1 inhibitors specifically potentiated intra-tumoral T cell activation, promoting an effector memory-like T cell phenotype without systemic cytokine secretion in a variety of syngeneic and human tumor xenograft models. Combining this class of CD28-co-stimulatory bispecific antibodies with the clinically validated anti-PD-1 treatment provides a well-tolerated antibody therapy with markedly enhanced anti-tumor efficacy.

EGFR x CD28 multispecific antibodies

Antigen binding molecules (ABMs) comprising Fab domains in non-native configurations, ABM conjugates comprising the ABMs and cytotoxic or cytostatic agents, pharmaceutical compositions containing the ABMs and ABM conjugates, methods of using the ABMs, ABM conjugates and pharmaceutical compositions for treating cancer, nucleic acids encoding the ABMs, cells engineered to express the ABMs, and methods of producing ABMs.

Antigen binding molecule formats

The present disclosure relates to IL2 agonists with improved therapeutic profiles.

IL2 agonists and methods of use thereof

The present invention provides compositions and methods for treating cancer and inhibiting cytokine release syndrome (CRS). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of a CD40 antagonist or a CAR-T cell expressing a CD40 antagonist in combination with a therapeutically effective amount of a CD3 multispecific antigen binding molecule.

Compositions and methods for treating cytokine release syndrome

Multispecific binding molecules (MBMs) comprising an N-terminal scFv, a first Fab and a second Fab, MBM conjugates comprising the MBMs and cytotoxic or cytostatic agents, pharmaceutical compositions containing the MBMs and MBM conjugates, methods of using the MBMs, MBM conjugates and pharmaceutical compositions for treating cancer, nucleic acids encoding the MBMs, cells engineered to express the MBMs, and methods of producing MBMs.

N-terminal scFv multispecific binding molecules

IgG Fc-IL2-Rα-IL2 fusions and methods of use thereof

IL2 and peptide-MHC complex fusion proteins and methods of use thereof

The present invention provides multispecific antigen-binding molecules that bind both a T-cell antigen (e.g., CD3) and a target antigen (e.g., a tumor associated antigen, a viral or bacterial antigen), and which include a single polypeptide chain that is multivalent (e.g., bivalent) with respect to T-cell antigen binding, and uses thereof.

Multispecific antigen-binding molecules for cell targeting and uses thereof

Growing community of inventors

Scarsdale, NY, United States of America

Chia-Yang Lin