Regeneron Pharmaceuticals, Inc.

Amgen Inc.

Regeneran Pharmaceuticals, Inc.

Kara Olson

Eric L Smith

Samuel H Davis

Douglas MacDonald

Andrew J Murphy

Olga Sineshchekova

Gavin Thurston

Ka-Man Venus Lai

Jessica Kirshner

David DiLillo

Dayong Guo

Frank Delfino

Aynur Hermann

Kenneth Allan Brasel

Erica Ullman

Dauphine S Barone

Qian Zhang

Jose Carlos Escobar

Jacqueline A Kirchner

George D Yancopoulos

Eric B Smith

Chia-Yang Lin

Dimitris Skokos

Janelle Waite

Joyce Wei

David Dilillo

Non-human animals, expressing humanized CD3 proteins are provided. Non-human animals, e.g., rodents, genetically modified to comprise in their genome humanized CD3 proteins are also provided. Additionally, provided are methods and compositions of making such non-human animals, as well as methods of using said non-human animals.

Non-human animals expressing humanized CD3 complex

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

B-cell maturation antigen (BCMA) is expressed on malignant plasma cells. The present invention provides novel bispecific antibodies (bsAbs) that bind to both BCMA and CD3 and activate T cells via the CD3 complex in the presence of BCMA-expressing tumor cells. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing BCMA. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced BCMA-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including multiple myeloma.

Nucleic acid molecules encoding bispecific anti-BCMA x anti-CD3 antibodies

A bispecific antibody format providing ease of isolation is provided, comprising immunoglobulin heavy chain variable domains that are differentially modified in the CH3 domain, wherein the differential modifications are non-immunogenic or substantially non-immunogenic with respect to the CH3 modifications, and at least one of the modifications results in a differential affinity for the bispecific antibody for an affinity reagent such as Protein A, and the bispecific antibody is isolable from a disrupted cell, from medium, or from a mixture of antibodies based on its affinity for Protein A.

Readily isolated bispecific antibodies with native immunoglobulin format

CD38 is expressed on malignant plasma cells. CD28 is a costimulatory molecule required for T-cell activation and survival. Provided herein are novel anti-CD38 antibodies, anti-CD28 antibodies, and bispecific antibodies (bsAbs) that bind to both CD38 and CD28 and act as costimulatory agents to activate T cells via binding CD80 and/or CD86. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing CD38. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced CD38-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including multiple myeloma, lymphoma, and leukemia.

Antigen-binding molecules that bind CD38 and/or CD28, and uses thereof

The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human CD-22. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing CD-22, such as B-cell lymphomas. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.

Bispecific anti-CD28 &#xd7; anti-CD22 antibodies and uses thereof

Bispecific anti-BCMA x anti-CD3 antibodies and uses thereof

Antigen binding proteins that bind to human GM-CSF protein are provided. Nucleic acids encoding the antigen binding protein, vectors, and cells encoding the same are also provided. The antigen binding proteins can inhibit binding of GM-CSF to GM-CSFR, inhibit GM-CSF-induced proliferation and signaling of myeloid lineage cell lines and inhibit GM-CSF-induced activation of human monocytes.

Nucleic acid molecule encoding human GM-CSF antigen binding proteins

Human GM-CSF antigen binding proteins

Growing community of inventors

White Plains, NY, United States of America

Kara Olson