Compartmentalized assays of bispecific and multispecific biologics

Abstract

A method for performing assays in compartmentalized nano-volumes to screen for functional bispecific or multispecific biologics, including: obtaining a plurality of at least two distinct types of cells, wherein a first-type of cells are engineered to express a single genetic-variant per cell of a bispecific or multispecific biologic in a secreted form, and wherein a second-type of cells are selected or engineered to produce a positive reporter molecule signal that is triggered by a functional variant of the bispecific or multispecific biologic expressed from the single genetic-variant by the first-type cell, wherein the bispecific or multispecific biologic has target-binding moieties that bind to two different target molecules on the same cell or to two different epitopes of the same target molecule that leads to clustering, endocytosis (internalizing) and/or degradation of the bispecific or multispecific biologic and/or the target molecule(s); co-encapsulating into each of a plurality of compartmentalized nano-volumes only one cell of the first-type cell and one or more cell(s) of the second-type cell; incubating the nano-volumes over a period of time sufficient to allow the expression and secretion of the bispecific or multispecific biologic, clustering, endocytosis (internalizing) and/or degradation of the bispecific or multispecific biologic and/or target molecule(s) and expression of the positive reporter molecule signal inside the nano-volumes; collecting data representing a positive reporter molecule signal triggered by the secreted bispecific or multispecific biologics inside the nano-volumes, recovering the first type of cells from the nano-volumes that exhibit a positive reporter molecule signal, and extracting from the recovered first type of cells genetic information representing respective functional variants of the bispecific or multispecific biologics.

Dependencies are inferred from the claim text.