Monitoring health and disease status using clonotype profiles

Patent metadata

Field	Value
Publication number	US-12209282-B2
Application number	US-202117316148-A
Country	US
Kind code	B2
Filing date	May 10, 2021
Priority date	Nov 7, 2008
Publication date	Jan 28, 2025
Grant date	Jan 28, 2025

Abstract

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.

First claim

What is claimed is:

1. A method of monitoring a cancer in a patient by one or more patient-specific clonotypes correlated with the cancer, the method comprising the steps of:
(a) amplifying in a multiplex polymerase chain reaction (PCR) recombined nucleic acids comprising complementary determining region 3 (CDR3) sequences from immunoglobulin genes or T cell receptor (TCR) genes from a sample of nucleic acids from B cells and/or T cells obtained from the patient, wherein the sample is from a tissue affected by the cancer;
(b) sequencing the amplified nucleic acids by high-throughput sequencing (HTS) to form a clonotype profile, wherein the clonotype profile comprises at least 10,000 clonotype sequences of 20 to 400 nucleotides in length;
(c) determining from the clonotype profile one or more patient-specific clonotypes correlated with the cancer; and
(d) monitoring a level of the one or more patient-specific clonotypes in one or more samples subsequently obtained from the patient.

2. The method according to claim 1 , wherein the cancer is lymphoid cancer.

3. The method according to claim 2 , wherein the lymphoid cancer is B-cell acute lymphoblastic leukemia (ALL).

4. The method according to claim 3 , wherein step (a) comprises amplifying recombined nucleic acids comprising CDR3 sequences from immunoglobulin genes from a sample comprising B cells obtained from the patient.

5. The method according to claim 4 , wherein the sample comprising B cells obtained from the patient comprises bone marrow.

6. The method according to claim 5 , wherein the recombined nucleic acids comprise VDJ rearrangements of IgH genes, DJ rearrangements of IgH genes, rearrangements of IgK genes, rearrangements of IgL genes, BCL1-IgH translocations, BCL2-IgH translocations, or any combination thereof.

7. The method according to claim 5 , wherein the one or more samples subsequently obtained from the patient comprise one or more bone marrow samples.

8. The method according to claim 5 , wherein the one or more samples subsequently obtained from the patient comprise one or more peripheral blood samples.

9. The method according to claim 2 , wherein the lymphoid cancer is multiple myeloma (MM).

10. The method according to claim 9 , wherein step (a) comprises amplifying recombined nucleic acids comprising CDR3 sequences from immunoglobulin genes from a sample comprising B cells obtained from the patient.

11. The method according to claim 10 , wherein the sample comprising B cells obtained from the patient comprises bone marrow.

12. The method according to claim 11 , wherein the recombined nucleic acids comprise VDJ rearrangements of IgH genes, DJ rearrangements of IgH genes, rearrangements of IgK genes, rearrangements of IgL genes, BCL1-IgH translocations, BCL2-IgH translocations, or any combination thereof.

13. The method according to claim 11 , wherein the one or more samples subsequently obtained from the patient comprise one or more bone marrow samples.

14. The method according to claim 11 , wherein the one or more samples subsequently obtained from the patient comprise one or more peripheral blood samples.

15. The method according to claim 2 , wherein the lymphoid cancer is chronic lymphocytic leukemia (CLL).

16. The method according to claim 15 , wherein step (a) comprises amplifying recombined nucleic acids comprising CDR3 sequences from immunoglobulin genes from a sample comprising B cells obtained from the patient.

17. The method according to claim 16 , wherein the sample comprising B cells obtained from the patient comprises peripheral blood or bone marrow.

18. The method according to claim 17 , wherein the recombined nucleic acids comprise VDJ rearrangements of IgH genes, DJ rearrangements of IgH genes, rearrangements of IgK genes, rearrangements of IgL genes, BCL1-IgH translocations, BCL2-IgH translocations, or any combination thereof.

19. The method according to claim 17 , wherein the one or more samples subsequently obtained from the patient comprise one or more bone marrow samples.

20. The method according to claim 17 , wherein the one or more samples subsequently obtained from the patient comprise one or more peripheral blood samples.

Assignees

• Adaptive Biotechnologies Corp

Inventors

• Faham Malek
• Willis Thomas

Classifications

• C12Q1/6874

  involving nucleic acid arrays, e.g. sequencing by hybridisation · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q1/6886

  for cancer (immunoassay for cancer G01N33/575) · CPC title