University of Texas System

Stcube, Inc.

Stcube & Co., Inc.

Stsciences, Inc.

Stephen Sunghan Yoo

Mien-Chie Hung

Yong-Soo Kim

Chia-Wei Li

Seung-Oe Lim

Ezra M Chung

Michael Joseph Surace

Yong-Sik Bong

Ezra Myung Chul Chung

Steven Hsesheng Lin

Andrew H Park

Amrish Sharma

Kyu Lee Han

Provided herein are methods for treating cancer using molecules having an antigen binding fragment that immunospecifically binds to BTN1A1, such as anti-BTN1A1 antibodies. These molecules include those having an antigen binding fragment that immunospecifically binds to glycosylated BTN1A1, such as anti-glycosylated BTN1A1 antibodies. Also included are molecules having an antigen binding fragment that immunospecifically bind to BTN1A1 dimers, such as anti-BTN1A1 dimer antibodies. Also provided are methods for treating anti-PD-1 therapy or anti-PD-L1 therapy resistant or refractory cancers.

Methods of treating cancer using antibodies and molecules that immunospecifically bind to BTN1A1

Methods for producing and screening for antibodies that specifically bind to glycosylated immune checkpoint proteins (ICPs) relative to non-glycosylated ICPs are provided. Such antibodies recognize specific epitopes of glycosylated ICPs and can prevent or block the binding of a glycosylated ICP with its ligand, such as another ICP, and can inhibit the interactions between the two proteins that can lead to immunosuppression, as exemplified by the human PD-L1/PD-1 interaction. By way of specific example, human PD-L1 and PD-1 polypeptides comprising glycosylated amino acid residues within their extracellular domains are provided for generating anti-glycosylated PD-L1 or anti-glycosylated PD-1 antibodies that specifically bind PD-L1 or PD-1, respectively, and inhibit the PD-L1/PD-1 interaction. The antibodies produced and selected by the methods are especially useful as cancer therapeutics for disrupting, blocking, or neutralizing the ICP system and specific ICP interactions therein.

Methods for selecting antibodies that specifically bind glycosylated immune checkpoint proteins

Antibodies that selectively bind to glycosylated PD-1 relative to unglycosylated PD-1 are provided. In some aspects, PD-1 polypeptides comprising glycosylated amino acid positions are also provided. Methods for making and using such antibodies and polypeptides (e.g., for the treatment of cancer) are also provided.

Antibodies specific to glycosylated PD-1 and methods of use thereof

Provided herein are molecules having an antigen binding fragment that immunospecifically binds to BTN1A1, such as anti-BTN1A1 antibodies. These molecules include those having an antigen binding fragment that immunospecifically binds to glycosylated BTN1A1, such as anti-glycosylated BTN1A1 antibodies. Methods of making and using these molecules are also provided, including methods of using them in cancer therapies, or as cancer diagnostics.

Antibodies and molecules that immunospecifically bind to BTN1A1 and the therapeutic uses thereof

Antibodies specific to glycosylated PD-L1 and methods of use thereof

Anti-cancer treatment and therapeutic methods are provided in which an antibody that binds specifically to glycosylated PD-L1 relative to unglycosylated PD-L1 and blocks binding of PD-L1 to PD-1 is administered to a subject in need in combination with an antibody that binds specifically to glycosylated PD-L1 relative to unglycosylated PD-L1, blocks binding of PD-L1 to PD-1 and also promotes internalization and degradation of PD-L1. The anti-cancer methods utilize antibodies that recognize specific epitopes on glycosylated PD-L1 protein, as well as antibodies that exhibit the IPD function of both blocking the binding of PD-L1 to PD-1 and also facilitating the internalization of PD-L1 on cells expressing PD-L1. Methods in which such antibody combinations are especially useful include cancer and tumor treatments and therapies in which the cancer or tumor is a PD-L1 positive cancer or tumor.

Methods of cancer treatment and therapy using a combination of antibodies that bind glycosylated PD-L1

Antibodies that bind specifically to glycosylated PD-L1 relative to unglycosylated PD-L1, block binding of PD-L1 to PD-1 and promote internalization and degradation of PD-L1 are provided. Antibodies that recognize specific epitopes on glycosylated PD-L1 protein and that exhibit the dual functions of both blocking the binding of PD-L1 to PD-1 and also facilitating the internalization of PD-L1 on cells are provided. In some aspects, PD-L1 polypeptides comprising glycosylated amino acid residues at amino and carboxy terminal positions of the PD-L1 extracellular domain are also provided. Methods for using such antibodies for the treatment of cancer, particularly PD-L1 positive cancer, are also provided.

Dual function antibodies specific to glycosylated PD-L1 and methods of use thereof

Provided herein are methods for treating cancer using molecules having an antigen binding fragment that immunospecifically binds to BTN1A1 or a BTN1A1 ligand, such as anti-BTN1A1 antibodies or anti-BTN1A1 ligand antibodies. Also provided herein are BTN1A1 ligands, such as Galectin-1, Galectin-9, Neuropilin-2, and B- and T-Lymphocyte Attenuator.

Methods of treating cancer using antibodies and molecules that bind to BTN1A1 or BTN1A1-ligands

Provided herein are molecules, such as antibodies, that selectively bind to glycosylated BTLA (B- and T-lymphocyte attenuator) relative to unglycosylated BTLA. Methods for making and using such molecules are also provided, including methods for treating or diagnosing cancer. In some embodiments, the anti-glycosylated BTLA antibodies provided herein can immunospecifically bind to glycosylated wild-type BTLA (WT). In some embodiments, the anti-glycosylated BTLA antibodies provided herein can immunospecifically bind to one or more BTLA double mutants that retain only a single glycosylation site at BTLA N75, N94 or N110. In some embodiments, the anti-glycosylated BTLA antibodies provided herein show only background binding, if any, to a BTLA triple mutant, that retains none of BTLA's N75, N94, or N110 0-glycosylation sites.

Antibodies specific to glycosylated BTLA (B- and T- lymphocyte attenuator)

Antibodies that bind specifically to glycosylated PD-L1 relative to unglycosylated PD-L1 are provided. Antibodies that recognize specific epitopes of glycosylated PD-L1 protein and can block the binding of PD-L1 to PD-1 are provided. In some aspects, PD-L1 polypeptides comprising glycosylated amino acid residues at amino and carboxy terminal positions of the PD-L1 extracellular domain are also provided. Methods for making and using such antibodies and polypeptides (e.g., for the treatment of cancer) are also provided.

Growing community of inventors

Centreville, VA, United States of America

Stephen Sunghan Yoo