Methods and processes for non-invasive assessment of genetic variations

Patent metadata

Field	Value
Publication number	US-10738359-B2
Application number	US-201715443051-A
Country	US
Kind code	B2
Filing date	Feb 27, 2017
Priority date	Mar 2, 2012
Publication date	Aug 11, 2020
Grant date	Aug 11, 2020

Abstract

Technology provided herein relates in part to methods, processes and apparatuses for non-invasive assessment of genetic variations.

First claim

What is claimed is:

1. A method for enriching tumor-derived nucleic acid species from a cell-free circulating sample nucleic acid, comprising:
(a) obtaining cell-free circulating sample nucleic acid from a biological sample from a subject, which sample nucleic acid comprises a normal nucleic acid species and a tumor-derived nucleic acid species; and
(b) separating some or substantially all molecules of the normal nucleic acid species from molecules of the tumor-derived nucleic acid species, thereby generating a separation product enriched for the tumor-derived nucleic acid species,
wherein separating some or substantially all molecules of the normal nucleic acid species from molecules of the tumor-derived nucleic acid species comprises contacting the sample nucleic acid with an agent that specifically binds to a histone associated with tumor-derived nucleic acids species, wherein the histone is selected from the group consisting of H1.1, H1.3, and H1.5,
wherein the tumor-derived nucleic acid species in the separation product is enriched relative to tumor-derived nucleic acid in the cell-free circulating sample nucleic acid and wherein the separation product comprises about 50% or greater tumor-derived nucleic acid species.

2. The method of claim 1 , comprising (c) analyzing nucleic acid in the separation product.

3. A method for enriching tumor-derived nucleic acid species from a cell-free circulating sample nucleic acid, comprising:
(a) obtaining cell-free circulating sample nucleic acid from a biological sample from a subject, which sample nucleic acid comprises a normal nucleic acid species and a tumor-derived nucleic acid species; and
(b) separating some or substantially all molecules of the normal nucleic acid species from molecules of the tumor-derived nucleic acid species, thereby generating a separation product enriched for the tumor-derived nucleic acid species,
wherein separating some or substantially all molecules of the normal nucleic acid species from molecules of the tumor-derived nucleic acid species comprises contacting the sample nucleic acid with an agent that specifically binds to a histone that is associated with normal nucleic acid species and wherein the histone is selected from the group consisting of H1b and H3.3
wherein the tumor-derived nucleic acid species in the separation product is enriched relative to tumor-derived nucleic acid in the cell-free circulating sample nucleic acid and wherein the separation product comprises about 50% or greater tumor-derived nucleic acid species.

4. The method of claim 3 , comprising (c) analyzing nucleic acid in the separation product.

5. The method of claim 3 , wherein the agent is an antibody.

6. The method of claim 1 , wherein the agent is an antibody.

7. The method of claim 1 , wherein the sample nucleic acid is from blood plasma.

8. The method of claim 1 , wherein obtaining the sample nucleic acid comprises subjecting the biological sample to an in vitro process that isolates the sample nucleic acid from other sample components.

9. The method of claim 8 , wherein the in vitro process comprises centrifugation.

10. The method of claim 2 , wherein analyzing nucleic acid in the preparation product comprises use of a sequencing process.

11. The method of claim 2 , comprising (d) determining the presence or absence of a genetic variation according to the analysis in (c).

12. The method of claim 3 , wherein the sample nucleic acid is from blood plasma.

13. The method of claim 3 , wherein obtaining the sample nucleic acid comprises subjecting the biological sample to an in vitro process that isolates the sample nucleic acid from other sample components.

14. The method of claim 8 , wherein the in vitro process comprises centrifugation.

15. The method of claim 4 , wherein analyzing nucleic acid in the preparation product comprises use of a sequencing process.

16. The method of claim 4 , comprising (d) determining the presence or absence of a genetic variation according to the analysis in (c).

Assignees

• Sequenom Inc

Inventors

• Cantor Charles R
• Desantis Grace
• Mueller Reinhold
• Ehrich Mathias

Classifications

• C12Q1/6804 Primary

  Nucleic acid analysis using immunogens (immunoassay G01N33/53) · CPC title

• C12Q1/68

  involving nucleic acids · CPC title

• C07K16/18

  against material from animals or humans · CPC title

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title