Antibodies Specific to Glycosylated PD-L1 and Methods of Use Thereof

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Inventors

Stephen S. Yoo, Ezra M. Chung, Yong-Soo KIm, Mien-Chie Hung, Chia-Wei Li, and Seung-Oe Lim

Assignees

  1. STCUBE, Inc., Seoul (KR);
  2. BOARD OF REGENTS, THE UNIVERSITY OF TEXAS, Austin, TX (US)

Abstract

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.

CovalX Technology Used

Epitope Mapping

Outcomes

Mouse monoclonal anti-glycPD-L1 antibody STM004 was epitope mapped using the CovalX epitope mapping service. It was investigated whether or not unstructured peptides generated by proteolysis of the PD-L1 antigen could inhibit the  inteitope-mapping-hdx-ms/raction between PD-L1 protein as a target antigen and the anti-glycPD-L1 antibodies. From the epitope mapping, it was also determined that anti-PD-L1 MAb STM004 recognizes an epitope on PD-L1 that is conformational. Specifically, it was found that STM004 binds to an epitope on PD-L1 that is in contact with the amino acid residues at Y56, K62 and K75 contained within residues 48 to 78. STM115 binds to an epitope on PD-L1 that is in contact with the amino acid residues at K62, H69 and K75 contained within the residues 61 to 78.

Patent Number

US2018/0118830 A1

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Categories : Patents, Epitope Mapping