University of Texas System

Stcube, Inc.

The Texas A&m University System

Stcube & Co., Inc.

Kuo Kwang Biotech Corporation

Mien-Chie Hung

Stephen Sunghan Yoo

Seung-Oe Lim

Chia-Wei Li

Yong-Soo Kim

Di-hua Yu

Ezra M Chung

Xiangming Xing

Dihua Yu

Keng-Li Lan

Zheng Li

Keng-Hsin Lan

Xiaoyan Zhou

Hua Chen

Jun Yang

Jun Yao

Wentao Yang

Ping Li

Naoto T Ueno

Xiaoming Xie

Christopher L Neal

Raphael E Pollock

Nina T Nguyen

Yujiao Joe Zhang

Yong Wen

Angabin Matin

Hsin-Wei Liao

Jung-Mao Hsu

Jaw-Ching Liu

Chi-Ping Day

Kun-Ming Rau

Yan E Wang

Yan Li

Yi Du

Jun Kameoka

Jaffer Ajani

Jim Klostergaard

Nan Jing

Ralph Wilfred Paul

Andrew H Park

Aaron Garth Loomis

Weiya Xia

Yiu-Keung Lau

Daniel Nathan Andrew LaFoc

Kyu Lee Han

Duen-Hwa Yan

Bill Spohn

Chao-Kai Chou

Toshihiko Utsumi

Angahin Matin

Fu Ou Yang

Fu Ou-Yang

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

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

This invention provides biomarkers (e.g., methylation of R198 or R200 of EGFR or the presence of an arginine at position 497 of EGFR) for the prediction of resistance to cetuximab therapy. This invention also provides methods for the selection of patients for combination therapy with cetuximab and PRMT inhibitors.

Detection of arginine methylation of EGFR for prediction of resistance to therapy

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.

Provided herein are methods for identifying and treating cancers that are resistant to PARP inhibition. Methods for sensitizing cancers to a PARP inhibitor therapy are also provided. In some aspects. PARP inhibitor cancers are treated with a PARP inhibitor therapy in combination with a c-Met inhibitor therapy.

Prediction of response to PARP inhibitors and combinational therapy targeting C-MET and PARP1

Methods and composition for tumor therapy, especially esophageal adenocarcinoma (EAC), are described. For example, in certain aspects methods for determining Hedgehog and mTOR signaling pathway status to select patients for administering a combination therapy of Hedgehog and mTOR signaling inhibitors are described. Furthermore, the invention provides compositions that involve testing kits for determining signaling status.

Personalized medicine for the prediction of therapy targeting the hedgehog pathway

A single molecule or molecule complex detection method is disclosed in certain aspects, comprising nano- or micro-fluidic channels.

Methods for detecting molecule-molecule interactions with a single detection channel

The present invention regards mutant forms of Bik that comprise anti-cell proliferation and/or pro-apoptotic activities. In particular embodiments, the Bik polypeptides comprise a substitution at Thr33 and Ser35 and, in some embodiments, phosphorylation at these sites is inhibited. In more particular embodiments, these forms are useful for cancer therapy, particularly when administered in combination with liposomes. In embodiments wherein a mutant Bik polynucleotide is administered for cancer therapy, the polynucleotide may be regulated in a tissue-specific manner.

Antitumor effect of mutant Bik

The present invention is directed to compositions comprising an angiogenesis inhibitor coupled to a therapeutic or diagnostic agent. In a specific embodiment, the composition is a fusion gene or fusion gene product encoding the angiogenesis inhibitor coupled to a therapeutic or diagnostic agent. In a particular embodiment, the composition is used for methods to treat angiogenesis-related diseases, such as cancer.

Targeting proteins to deliver therapeutic or diagnostic reagents

Growing community of inventors

Houston, TX, United States of America

Mien-Chie Hung