	US 12,227,804 B2
	Determining a nucleic acid sequence imbalance associated with cancer using multiple markers
Yuk-Ming Dennis Lo, Kowloon (CN); Rossa Wai Kwun Chiu, Shatin (CN); Kwan Chee Chan, Shatin (CN); Benny Chung Ying Zee, Ma On Shan (CN); and Ka Chun Chong, Tai Po (CN)
Assigned to The Chinese University of Hong Kong, Shatin (HK)
Filed by The Chinese University of Hong Kong, Shatin (HK)
Filed on Oct. 31, 2019, as Appl. No. 16/670,981.
Application 16/246,420 is a division of application No. 14/030,904, filed on Sep. 18, 2013, granted, now 10,208,348, issued on Feb. 19, 2019.
Application 14/030,904 is a division of application No. 12/178,116, filed on Jul. 23, 2008, granted, now 8,706,422, issued on Apr. 22, 2014.
Application 16/670,981 is a continuation of application No. 16/246,420, filed on Jan. 11, 2019, granted, now 11,725,245.
Claims priority of provisional application 60/951,438, filed on Jul. 23, 2007.
Prior Publication US 2020/0056242 A1, Feb. 20, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C12Q 1/6883 (2018.01); C12Q 1/6827 (2018.01); C12Q 1/6888 (2018.01); G16B 20/00 (2019.01); G16B 20/10 (2019.01); G16B 20/20 (2019.01); G16B 30/00 (2019.01)

CPC C12Q 1/6883 (2013.01) [C12Q 1/6827 (2013.01); C12Q 1/6888 (2013.01); G16B 20/00 (2019.02); G16B 20/10 (2019.02); G16B 20/20 (2019.02); C12Q 2600/112 (2013.01); C12Q 2600/154 (2013.01); C12Q 2600/156 (2013.01); G01N 2800/387 (2013.01); G16B 30/00 (2019.02); Y02A 90/10 (2018.01)]

27 Claims

1. A method for determining whether a nucleic acid sequence imbalance associated with cancer exists within a biological sample from a subject, the biological sample including cell-free nucleic acid molecules originating from non-malignant cells and potentially from tumor cells associated with cancer, the method comprising:

separating the cell-free nucleic acid molecules of the biological sample into a plurality of reactions;

measuring signals from the plurality of reactions;

receiving, at a computer system, first quantitative data indicating a first total amount of a plurality of clinically relevant nucleic acid sequences in the plurality of reactions involving cell-free nucleic acid molecules from the biological sample;

receiving, at the computer system, second quantitative data indicating a second total amount of a plurality of background nucleic acid sequences in the plurality of reactions, wherein the plurality of background nucleic acid sequences is different from any one of the plurality of clinically relevant nucleic acid sequences, wherein the measured signals include the first quantitative data and the second quantitative data;

determining, at the computer system, the first total amount of the plurality of clinically relevant nucleic acid sequences from the first quantitative data;

determining, at the computer system, the second total amount of the plurality of background nucleic acid sequences from the second quantitative data;

determining a parameter from the first total amount and the second total amount, wherein the parameter is based on a numerical value characterizing the first total amount and the second total amount; and

based on the parameter, determining a classification of whether the nucleic acid sequence imbalance associated with cancer exists in the biological sample for the plurality of clinically relevant nucleic acid sequences in the subject.