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Publication Number
US-10222369-B2
Publication Date
2019-03-05
Expiration Date
Abstract
The present invention relates generally to the field of making novel antigen binding domains against infectious diseases. The present invention also relates to novel CARs that utilize the novel antigen binding domains as an extracellular element. The present invention also relates to use of the novel antigen binding domains as therapeutic agents.
Core Innovation
The described invention provides a platform for finding a chimeric antigen receptor (CAR) that is activated by an antigen using a plurality of eukaryotic cells that collectively display a plurality of different antigen binding domains. Each eukaryotic cell comprises a nucleic acid encoding an antigen binding domain operably linked to a polynucleotide encoding a CAR chassis that includes a transmembrane element and an intracellular element.
The method mixes the antigen with the plurality of eukaryotic cells and incubates the eukaryotic cells with the antigen, and then identifies a eukaryotic cell that is activated in the presence of the antigen, thereby identifying the CAR that is activated by the antigen. The plurality of eukaryotic cells collectively display different antigen binding domains, enabling selection of antigen-activated CAR function from the displayed domain set.
The disclosed approach also includes CAR chassis and nucleic-acid control features, including CAR forms such as Smart-CAR, DE-CAR, Smart-DE-CAR, and Side-CAR. These include optional RNA control devices and destabilizing elements operably linked with the polynucleotide encoding the CAR chassis to regulate CAR expression and/or activity, while maintaining the basic antigen-driven CAR activation and identification workflow.
Claims Coverage
Independent claim clm-00001 covers a method for finding an antigen-activated CAR using a CAR/chassis library displayed on a plurality of eukaryotic cells, with activation identification based on antigen presence. The independent-claim coverage includes four inventive features centered on collective display of multiple antigen binding domains, operable linkage to a CAR chassis, antigen exposure, and identification of activated cells to identify the activated CAR. Dependent claims refine these features with specific cell types, antigen contexts, and additional CAR regulatory components.
Collective display of diverse antigen binding domains on eukaryotic cells
Providing a plurality of eukaryotic cells wherein each eukaryotic cell comprises a nucleic acid comprising a polynucleotide encoding an antigen binding domain, and wherein the plurality of eukaryotic cells collectively display a plurality of different antigen binding domains.
Antigen-binding domain operably linked to a CAR chassis with transmembrane and intracellular elements
Providing a polynucleotide encoding a CAR chassis comprised of a transmembrane element and an intracellular element, wherein the transmembrane element is linked to the intracellular element, and wherein the polynucleotide encoding the antigen binding domain is operably linked to the polynucleotide encoding the CAR chassis.
Antigen mixing/incubation and activation-based identification of an activated CAR
Mixing the antigen with the plurality of eukaryotic cells; incubating the plurality of eukaryotic cells with the antigen; and identifying a eukaryotic cell that is activated in the presence of the antigen, whereby the CAR that is activated by the antigen is identified.
RNA control device linked to the CAR chassis
Further includes a polynucleotide encoding an RNA control device operably linked to the polynucleotide encoding the CAR chassis.
Destabilizing element linked to the CAR chassis
Further includes that the nucleic acid comprises a polynucleotide encoding a destabilizing element that is operably linked to a polynucleotide encoding the CAR chassis.
Infectious disease causing agent antigen context
The antigen is part of an infectious disease causing agent and wherein the antigen mixed with the eukaryotic cell includes the infectious disease causing agent.
Overall claim coverage centers on identifying an antigen-activated CAR by using a plurality of eukaryotic cells collectively displaying diverse antigen binding domains and carrying a CAR chassis with transmembrane and intracellular elements, then selecting the activated cells after antigen exposure. Dependent features further specify eukaryotic cell types, add an RNA control device and/or a destabilizing element, and define antigen context as an infectious disease causing agent.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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