La Jolla Institute for Allergy and Immunology

Sanford Burnham Prebys Medical Discovery Institute

Kyowa Hakko Kirin Co., Limited

Pfizer Corporation

Sanford-burnham Medical Research Institute

Kyowa Hakko Kirin

Carl F Ware

John Sedy

Shinichiro Kato

Timothy C Cheung

Steven W Granger

Marcos Steinberg

Brian Miller

Michael Croft

Natasha K Crellin

Tigran Aivazian

Carl De Trez

Alessandro D Sette

Shahram Salek-Ardakani

Karen G Potter

Christopher A Benedict

Mitchell Kronenberg

Paula Norris

Magdalini Moutaftsi

Theresia A Banks

Ian R Humphreys

The present invention is based on the seminal discovery that BTLA agonist fusion proteins modulate an immune response. Specifically, the present invention provides fusion proteins that bind BTLA enhancing BTLA signaling. The present invention further provides methods of treating cancer and immune and inflammatory diseases and disorders with a BTLA agonist fusion protein as described herein.

BTLA fusion protein agonists and uses thereof

Ligand-specific HVEM variants, compositions comprising such variants, and methods of treating inflammatory diseases comprising administering such variants, are provided.

Compositions and methods for treating autoimmune and inflammatory disorders

The present invention relates to the seminal discovery that BTLA agonist antibodies modulate the immune system. Specifically, the present invention provides antibodies which bind BTLA in the activated state enhancing BTLA signaling. The present invention further provides methods of treating immune and inflammatory diseases and disorders with a BTLA agonist antibody.

Modulation of immune response using BTLA agonist antibodies

The present invention relate to the discovery that BTLA, IL-7 and ROR&#x3b3;t modulate the activity and expression of &#x3b3;&#x3b4;T cells. Specifically, the present invention provides methods of modulating &#x3b3;&#x3b4;T cell homeostasis and function by regulating expression of BTLA. The present invention further provides agents which modulate the activity and expression of BTLA, RORyt and IL-7 and methods for screening of such agents. The present invention also provides methods for treating autoimmune or inflammatory diseases using modulators of BTLA, RORyt and IL-7.

Modulation of &#x3b3;&#x3b4; T cells

The invention provides HVEM cis complexes which include, for example, HVEM/BTLA, HVEM/CD160 and HVEM/gD cis complexes. The invention provides ligands and agents that bind to HVEM cis complexes, such as antibodies. The invention further provides methods of use of the HVEM cis complexes, and the ligands and agents (e.g., LIGHT polypeptide sequence) that bind to the HVEM cis complexes.

Methods of modulating HVEM, BTLA and CD160 cis complex response or signaling activity with soluble light polypeptide sequences

The invention relates to compositions and methods that employ OX40 (CD134), a TNFR superfamily protein, agonists. The invention includes among other things administering an OX40 agonist alone or in combination with a viral antigen, or live or attenuated virus, to treat a viral infection, or for vaccination or immunization.

Virus vaccination and treatment methods with OX40 agonist compositions

Provided herein are antibodies that immunospecifically bind to an hLIGHT polypeptide; isolated nucleic acids encoding the antibodies; vectors and host cells comprising nucleic acids encoding the antibodies; methods of making the antibodies; and a method of treating a hLIGHT-mediated disease in a subject comprising administering to the subject the antibodies. In preferred embodiments, the anti-hLIGHT antibodies provided herein will ameliorate, neutralize or otherwise inhibit hLIGHT biological activity in vivo (e.g., the hLIGHT-mediated production or secretion of CCL20, IL-8 or RANTES from a cell expressing a hLIGHT receptor). Also provided herein is a method for the detection of hLIGHT in a sample as well as a method for ameliorating, neutralizing or otherwise inhibiting hLIGHT activity, e.g., in a human subject suffering from a disorder in which hLIGHT activity is detrimental.

Antagonistic human light-specific human monoclonal antibodies

The invention provides HVEM cis complexes which include, for example, HVEM/BTLA, HVEM/CD160 and HVEM/gD cis complexes. The invention provides ligands and agents that bind to HVEM cis complexes, such as antibodies. The invention further provides methods of use of the HVEM cis complexes, and the ligands and agents (e.g., antibodies) that bind to the HVEM cis complexes.

HVEM/BTLA, HVEM/CD 160 and HVEM/gD cis complexes and methods of use

The tumor-necrosis factor superfamily member LIGHT (p30; TNFSF-14) is a cytokine for inducing immune responses against tumors. A novel biochemical approach is used to decorate the surface of tumor cells with LIGHT. LIGHT decorated cells can be used to vaccinate and induce effective, sustained immunity against cells expressing neo or pathogen associated antigens. Variants of LIGHT are described that enhance binding to cellular receptors (e.g., LT beta receptor) and decrease regulation by inhibitors (e.g., Decoy Receptor 3) increasing ability to stimulate immunity.

Light-mediated anti-cell proliferative compositions and methods

Antagonistic human LIGHT-specific human monoclonal antibodies

Herpesvirus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and acts as a molecular switch that modulates T cell activation by propagating positive signals from the TNF related ligand, LIGHT (p30, TNFSF14), or inhibitory signals through the immunoglobulin superfamily member, B and T lymphocyte attenuator (BTLA). A novel binding site for BTLA is disclosed, located in cysteine-rich domain-1 of HVEM. BTLA binding site on HVEM overlaps with the binding site for the Herpes Simplex virus-1 envelope glycoprotein D (gD), but is distinct from where LIGHT binds, yet gD inhibits the binding of both ligands. A BTLA activating protein present in human cytomegalovirus is identified as UL144. UL144 binds BTLA, but not LIGHT, and inhibits T cell proliferation.

Growing community of inventors

Solana Beach, CA, United States of America

Carl F Ware