Regeneron Pharmaceuticals, Inc.

Regeneran Pharmaceuticals, Inc.

Dimitris Skokos

Andrew J Murphy

George D Yancopoulos

Eric L Smith

William C Olson

Israel Lowy

Lauric Haber

Aynur Hermann

Erica Ullman

Bei Wang

Janelle Waite

Frank Delfino

Robert Babb

Chia-Yang Lin

Brendan J Classon

Drew Dudgeon

Yu Huang

Matthew Sleeman

Rosalynn Molden

Eric B Smith

Kara Olson

Alison Crawford

Joyce Wei

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 PSMA. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing PSMA, such as prostate tumors. 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-PSMA x anti-CD28 antibodies and uses thereof

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

Provided herein are antibodies, and antigen-binding fragments thereof that specifically bind glucocorticoid-induced tumor necrosis factor receptor (GITR), compositions comprising the antibodies or antigen-binding fragments thereof, and methods of using the same, including, e.g., methods of treatment using the same.

Therapeutic uses of anti-GITR antibodies

EGFR × CD28 multispecific antibodies

Anti-GITR antibodies and uses thereof

Bispecific anti-PSMA X anti-CD28 antibodies 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 MUC16. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing MUC16, such as ovarian tumors. 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-MUC16 x anti-CD28 antibodies and uses thereof

Provided herein are antibodies, and antigen-binding fragments thereof that specifically bind glucocorticoid-induced tumor necrosis factor receptor (GITR) and methods of using the same, including, e.g., methods of treatment using the same.

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

A fully human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human TNF-like ligand 1A (hTL1A) is provided. The human anti-hTL1A antibodies are useful in treating diseases or disorders associated with TL1A, such as inflammatory diseases or disorders, e.g., inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, rheumatoid arthritis, and the like; autoimmune diseases or disorders, such as multiple sclerosis, diabetes, and the like; and allergic reactions, such as asthma and allergic lung inflammation.

Method of treating a TL1A-associated disease or disorder with human antibodies to TL1A

The present invention provides methods of preventing, treating or ameliorating diabetes by administering to a subject in need thereof a therapeutically effective amount of Dll4 antagonists that block Dll4-Notch signal pathways. As observed in a mouse model of diabetes, Dll4 antagonists exhibit protective effects on pancreatic islets, lower blood glucose levels, and block the production of auto-antibodies, including those against insulin and glutamic acid decarboxylase 65 (GAD65), via the expansion of regulatory T cells (Tregs). Thus, the present invention further provides methods of lowering the levels of blood glucose, and/or reducing or blocking the production of auto-antibodies, by administering to a subject in need thereof a therapeutically effective amount of Dll4 antagonists. Suitable Dll4 antagonists for the invention include antibodies or antibody fragments that specifically bind Dll4 and block Dll4-Notch interactions, the extracellular domain of Dll4, and the like.

Methods of treating diabetes with Dll4 antagonists

The present invention provides methods of treating a disease or disorder, in which increasing the number of regulatory T cell (Treg) is beneficial, by administering to a subject suffering from such a disease or disorder a therapeutically effective amount of Dll4 antagonists that block Dll4-Notch signal pathways, thereby increasing the number of Treg. Diseases or disorders treatable by the methods of the invention include autoimmune diseases or disorders, such as multiple sclerosis (MS), diabetes, and the like. Suitable Dll4 antagonists for the invention include antibodies or antibody fragments that specifically bind Dll4 and block Dll4-Notch interactions, the extracellular domain of Dll4, and the like. The invention also provides methods of preventing an occurrence or recurrence of such diseases or disorders in a subject predisposed or susceptible to developing such diseases or disorders. Furthermore, the methods of the invention are useful in preventing or treating organ transplant rejections or graft-versus-host disease.

Methods of treating autoimmune diseases with Dll4 antagonists

Human antibodies to human TNF-like ligand 1A (TL1A)

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New York, NY, United States of America

Dimitris Skokos