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US 2024/0192225 A1Published application
Method for epitope binning of novel monoclonal antibodies
Assignee10x Genomics, Inc.
InventorsWyatt James MCDONNELL, Michael John Terry STUBBINGTON, Ravi RAMENANI
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Abstract
The present disclosure generally relates to methods and systems for obtaining epitope specify of candidate antibodies against one or more known antibodies. Further, the present disclosure also provides systems and methods for epitope binning.
Claims98
A method, comprising:
- (a) obtaining a first epitope specificity of a first plurality of cells and a second epitope specificity of a second plurality of cells by contacting an antigen with the first plurality of cells and the second plurality of cells, wherein the antigen is labeled with a reporter oligonucleotide comprising a reporter sequence, and wherein the first plurality of cells is engineered to express a known antibody and the second plurality of cells is engineered to express a candidate antibody;
- (b) generating,
- i). a first reduced dimension representation of the first epitope specificity of the first plurality of cells expressing the known antibody;
- and
- ii). a second reduced dimension representation of the second epitope specificity of the second plurality of cells expressing the candidate antibody;
- (c) determining, based at least on the first reduced dimension representation and the second reduced dimension representation, whether the second plurality of cells exhibit a novel epitope specificity or an epitope specificity associated with the first plurality of cells.
3 more elements
A method, comprising:
- (a) obtaining a first epitope specificity of a first plurality of cells and a second epitope specificity of a second plurality of cells by contacting an antigen with the first plurality of cells and the second plurality of cells, wherein the antigen is labeled with a reporter oligonucleotide comprising a reporter sequence, and wherein the first plurality of cells is engineered to express a known antibody and the second plurality of cells is engineered to express a candidate antibody;
- and
- (b) applying, by at least one data processor, one or more data analysis techniques to determine whether the second plurality of cells exhibit a novel epitope specificity or an epitope specificity associated with the first plurality of cells.
A system comprising:
- at least one data processor;
- and
- at least one memory storing instructions, which when executed by the at least one data processor, result in operations comprising:
- generating, based at least on a first dataset indicating a first epitope specificity of a first plurality of cells expressing a known antibody, a first reduced dimension representation of the first dataset;
- generating, based at least on a second dataset indicating a second epitope specificity of a second plurality of cells expressing a candidate antibody, a second reduced dimension representation of the second dataset;
- and
- determining, based at least on the first reduced dimension representation and the second reduced dimension representation, whether the second plurality of cells exhibit a novel epitope specificity or an epitope specificity of the epitope bin associated with the first plurality of cells.
4 more elements
A computer-implemented method, comprising:
- generating, based at least on a first dataset indicating a first epitope specificity of a first plurality of cells expressing a known antibody, a first reduced dimension representation of the first dataset;
- generating, based at least on a second dataset indicating a second epitope specificity of a second plurality of cells expressing a candidate antibody, a second reduced dimension representation of the second dataset;
- and
- determining, based at least on the first reduced dimension representation and the second reduced dimension representation, whether the second plurality of cells exhibit a novel epitope specificity or an epitope specificity of the epitope bin associated with the first plurality of cells.
1 more element
A non-transitory computer readable medium storing instructions, which when executed by at least one data processor, result in operations comprising:
- generating, based at least on a first dataset indicating a first epitope specificity of a first plurality of cells expressing a known antibody, a first reduced dimension representation of the first dataset;
- generating, based at least on a second dataset indicating a second epitope specificity of a second plurality of cells expressing a candidate antibody, a second reduced dimension representation of the second dataset;
- and
- determining, based at least on the first reduced dimension representation and the second reduced dimension representation, whether the second plurality of cells exhibit a novel epitope specificity or an epitope specificity of the epitope bin associated with the first plurality of cells.
1 more element
A method, comprising:
- (a) generating a plurality of single cell suspensions, wherein each of the plurality of single cell suspensions comprises one of either a first plurality of cells or a second plurality of cells bound to or not bound to the antigen;
- (b) generating a library of barcoded nucleic acid molecules from the first plurality of cells and the second plurality of cells, wherein the library of barcoded nucleic acid molecules comprises a reporter sequence or complement thereof and sequences corresponding to immune receptors;
- (c) sequencing the library of barcoded nucleic acid molecules;
- (d) obtaining a first epitope specificity of the first plurality of cells and a second epitope specificity of the second plurality of cells by contacting the antigen with the first plurality of cells and the second plurality of cells, wherein the antigen is labeled with a reporter oligonucleotide comprising the reporter sequence, and wherein the first plurality of cells is engineered to express a known antibody and the second plurality of cells is engineered to express a candidate antibody;
- (e) generating,
- i). a first reduced dimension representation of the first epitope specificity of the first plurality of cells expressing the known antibody;
- and
- ii). a second reduced dimension representation of the second epitope specificity of the second plurality of cells expressing the candidate antibody;
- and
- (f) determining, based at least on the first reduced dimension representation and the second reduced dimension representation, whether the second plurality of cells exhibit a novel epitope specificity or an epitope specificity associated with the first plurality of cells.
7 more elements
Dependencies are inferred from the claim text.