Leland Stanford Junior University

University of California

Ab Initio Biotherapeutics, Inc.

The University of North Carolina at Chapel Hill

Vib Vzw

Vrije Universiteit Brussel

Friedrich-Alexander-Universitat Erlangen-Nürnberg

Friedrich-Alexander-universitÄt

Aashish Manglik

Aaron Michael Ring

Andrew Curtis Kruse

Brian K Kobilka

Roy Louis Maute

Irving L Weissman

Melissa N McCracken

Sydney Gordon

Brian K Shoichet

Peter Gmeiner

Daniela Gisela Dengler

Kenneth S Lin

Toon Laeremans

Jan Steyaert

Els Pardon

Bryan Leo Roth

Henry Lin

Harald Hübner

Anat Levit

Andrew Kruse

High affinity PD-1 mimic polypeptides are provided, which (i) comprise at least one amino acid change relative to a wild-type PD-1 protein; and (ii) have an increased affinity for PD-L1 relative to the wild-type protein. Compositions and methods are provided for modulating the activity of immune cells in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity PD-1 mimic polypeptide, which blocks the physiological binding interaction between PD-1 and its ligand PD-L1 and/or PD-L2.

High affinity PD-1 agents and methods of use

Described herein, inter alia, are compositions and methods for modulating mu opioid receptor activity.

Mu opioid receptor modulators

Provided herein are SIRP-gamma, SIRP-beta or SIRP-beta2 decoy polypeptides for immunotherapy and/or treatment of cancer, anemia, transplant, asthma, allergy, auto-immune disease, and viral infection.

SIRP-gamma polypeptide compositions and treatment of cancer

Agents that specifically bind to an opioid receptor in a conformationally specific way can be used to induce a conformational change in the receptor. Such agents have therapeutic applications and can be used in X-ray crystallography studies of the receptor. Such agents can also be used to improve drug discovery via compound screening and/or structure-based drug design.

Opioid receptor binding agents and uses thereof

Provided herein are several methods for selecting agents that bind to transmembrane receptors in a conformationally-selective way. In some embodiments, the method may comprise producing: a transmembrane receptor in an active conformation; and said transmembrane receptor in an inactive conformation and using cell sorting to select, from a population of cells comprising a library of cell surface-tethered extracellular capture agents, cells that are specifically bound to either the transmembrane receptor in its active conformation or the transmembrane receptor in its inactive conformation, but not both. In other embodiments, the method may comprise: contacting a GPCR with a population of cells that comprise a library of surface-tethered extracellular proteins; labeling the cell population with a conformationally-specific binding agent, e.g., a G-protein or mimetic thereof; and using cell sorting to select from the cell population cells that bind to the agent.

Compositions comprising G protein-coupled receptors maintained in a conformationally selective manner by a modulator

Methods and compositions are provided for displaying a protein of interest (POI) on the surface of a eukaryotic cell by fusing the POI to a signal polypeptide, a stalk polypeptide, and a surface anchor polypeptide to generate a surface accessible fusion protein. Nucleic acids are provided that include nucleotide sequences encoding a signal polypeptide, a stalk polypeptide, and a surface anchor polypeptide. In some cases, a subject nucleic acid includes and insertion site for the insertion of a POI. In some cases, a subject nucleic acid includes a nucleotide sequence that encodes a POI. In some cases a stalk polypeptide is a synthetic stalk polypeptide and various example synthetic stalk polypeptides are disclosed. In some cases, a surface anchor polypeptide is a glycosylphosphatidylinisotol (GPI) anchor domain, which can be synthetic. Kits are also provided for practicing the subject methods.

Compositions and methods for expressing polypeptides on the surface of cells

SIRP-gamma polypeptide compositions and methods of use

MU opioid receptor modulators

Complexes comprising transmembrane receptors and antibodies that bind the receptors in a conformationally selective manner

Method for selecting agents that bind to transmembrane receptors in a conformationally selective manner

SIRP polypeptide compositions and methods of use

Growing community of inventors

Menlo Park, CA, United States of America

Aashish Manglik