SEATTLE, WA, United States

Adaptive Biotechnologies Corporation

www.adaptivebiotech.com
SEATTLE, WA, United States
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Patent
Adaptive Biotechnologies Corporation | Date: 2017-02-08

The invention is directed to methods for determining antigen-specific lymphocytes, including T cells or B cells. In some embodiments, methods of the invention may be implemented by the steps of reacting under interaction conditions one or more antigens with lymphocytes in a plurality of subsets of a tissue sample, such as peripheral blood; sorting antigen-interacting lymphocytes from other lymphocytes; separately sequencing for each subset recombined nucleic acid encoding a segment of a TCR chain or BCR chain from a sample of T cells or B cells, respectively, prior to exposure to antigen and from a sample of T cells or B cells isolated based on their interaction with antigen, respectively, thereby forming a clonotype profile for the former sample and the latter sample for each subset; and identifying as antigen-specific lymphocytes those lymphocytes associated with a clonotype whose frequency increases in the latter sample relative to its frequency in the former sample.


Patent
Adaptive Biotechnologies Corporation and Fred Hutchinson Cancer Research Center | Date: 2017-02-22

A relative representation of adaptive immune cells in a biological sample is quantified using multiplex PCR and sequencing of adaptive immune cells, control genes, and synthetic template molecules. Disclosed herein are methods for quantifying a number of adaptive immune cells in a biological sample, and methods for quantifying a relative representation of adaptive immune cells in a biological sample that comprises a mixture of cells comprising adaptive immune cells and cells that are not adaptive immune cells. Methods are provided for amplifying by multiplex PCR and sequencing a first set of synthetic templates each comprising one TCR or IgV segment and one TCR of Ig J or C segment and a unique bar code.


Patent
Adaptive Biotechnologies Corporation | Date: 2017-03-22

There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer, especially lymphoid neoplasms, such as lymphomas and leukemias. Provided herein are methods for using DNA sequencing to identify personalized, or patient-specific biomarkers in patients with lymphoid neoplasms, autoimmune disease and other conditions. Identified biomarkers can be used to determine and/or monitor the disease state for a subject with an associated lymphoid disorder or autoimmune disease or other condition. In particular, the invention provides a sensitive method for monitoring lymphoid neoplasms that undergo clonal evolutions without the need to development alternative assays for the evolved or mutated clones serving as patient-specific biomarkers.


Patent
Adaptive Biotechnologies Corporation | Date: 2015-03-05

A relative representation of adaptive immune cells in a biological sample is quantified using multiplex PCR and sequencing of adaptive immune cells, control genes, and synthetic template molecules. Disclosed herein are methods for quantifying a number of adaptive immune cells in a biological sample, and methods for quantifying a relative representation of adaptive immune cells in a biological sample that comprises a mixture of cells comprising adaptive immune cells and cells that are not adaptive immune cells. Methods are provided for amplifying by multiplex PCR and sequencing a first set of synthetic templates each comprising one TCR or IgV segment and one TCR of Ig J or C segment and a unique bar code.


Patent
Adaptive Biotechnologies Corporation | Date: 2017-01-11

Methods are provided for correction of amplification bias and quantitation of adaptive immune cells in a sample using synthetic templates that include random oligonucleotide sequences.


Patent
Adaptive Biotechnologies Corporation and Fred Hutchinson Cancer Research Center | Date: 2016-06-27

Compositions and methods are disclosed for uniquely tagging each rearranged gene segment that encodes a T cell receptor (TCR) and/or an immunoglobulin (Ig), in a DNA (or mRNA or cDNA reverse transcribed therefrom) sample from lymphoid cells. These and related embodiments permit accurate, high throughput quantification of distinct TCR and/or Ig encoding sequences. Also provided are compositions and methods for quantitatively sequencing the genes that encode both chains of a TCR or Ig heterodimer in a single cell, for example, to characterize the degree of T or B cell clonality in a sample.


Patent
Adaptive Biotechnologies Corporation | Date: 2016-08-24

Methods are provided for producing monoclonal antibody candidates using adaptive immunity profiling. In some aspects, the method provides for the use of massively parallel signature sequencing.


Patent
Adaptive Biotechnologies Corporation | Date: 2016-03-04

There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer, especially lymphoid neoplasms, such as lymphomas and leukemias. Provided herein are methods for using DNA sequencing to identify personalized, or patient-specific biomarkers in patients with lymphoid neoplasms, autoimmune disease and other conditions. Identified biomarkers can be used to determine and/or monitor the disease state for a subject with an associated lymphoid disorder or autoimmune disease or other condition. In particular, the invention provides a sensitive method for monitoring lymphoid neoplasms that undergo clonal evolutions without the need to development alternative assays for the evolved or mutated clones serving as patient-specific biomarkers.


Compositions and methods are described for standardizing the DNA amplification efficiencies of a highly heterogeneous set of oligonucleotide primers as may typically be used to amplify a heterogeneous set of DNA templates that contains rearranged lymphoid cell DNA encoding T cell receptors (TCR) or immunoglobulins (IG). The presently disclosed embodiments are useful to overcome undesirable bias in the utilization of a subset of amplification primers, which leads to imprecision in multiplexed high throughput sequencing of amplification products to quantify unique TCR or Ig encoding genomes in a sample. Provided is a composition comprising a diverse plurality of template oligonucleotides in substantially equimolar amounts, for use as a calibration standard for amplification primer sets. Also provided are methods for identifying and correcting biased primer efficiency during amplification.


Patent
Adaptive Biotechnologies Corporation | Date: 2016-01-04

There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer. Provided herein are methods for using DNA sequencing to identify personalized biomarkers in patients with autoimmune disease and other conditions. Identified biomarkers can be used to determine the disease state for a subject with an autoimmune disease or other condition.

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