	US 12,131,802 B2
	Methods and apparatuses for predicting risk of prostate cancer and prostate gland volume
Andrew J. Vickers, Brooklyn, NY (US); Peter T. Scardino, New York, NY (US); Hans Lilja, New York, NY (US); Vincent Linder, Tewksbury, MA (US); and David Steinmiller, Mountain View, CA (US)
Assigned to OPKO Diagnostics, LLC, Woburn, MA (US); and Oy Arctic Partners Ab, Turku (FI)
Filed by OPKO Diagnostics, LLC, Woburn, MA (US); and Oy Arctic Partners Ab, Turku (FI)
Filed on Feb. 27, 2017, as Appl. No. 15/443,102.
Application 15/443,102 is a continuation of application No. 13/785,058, filed on Mar. 5, 2013, granted, now 9,672,329.
Claims priority of provisional application 61/606,554, filed on Mar. 5, 2012.
Claims priority of application No. 20125238 (FI), filed on Mar. 5, 2012.
Prior Publication US 2017/0168060 A1, Jun. 15, 2017
This patent is subject to a terminal disclaimer.
Int. Cl. G16B 20/00 (2019.01); B01L 3/00 (2006.01); C12Q 1/6886 (2018.01); G01N 33/543 (2006.01); G01N 33/574 (2006.01); G01N 33/68 (2006.01); G16B 40/00 (2019.01); G16H 10/40 (2018.01); G16H 50/20 (2018.01); G16H 50/30 (2018.01)

CPC G16B 20/00 (2019.02) [B01L 3/502 (2013.01); B01L 3/502715 (2013.01); B01L 3/502761 (2013.01); C12Q 1/6886 (2013.01); G01N 33/54366 (2013.01); G01N 33/57434 (2013.01); G01N 33/6893 (2013.01); G16B 40/00 (2019.02); G16H 10/40 (2018.01); G16H 50/20 (2018.01); G16H 50/30 (2018.01); B01L 2300/0654 (2013.01); B01L 2300/0816 (2013.01); B01L 2300/087 (2013.01); B01L 2400/0487 (2013.01); C12Q 2600/112 (2013.01); C12Q 2600/158 (2013.01); C12Q 2600/16 (2013.01); G01N 2333/96455 (2013.01)]

16 Claims

1. A method performed using an assay system, the assay system comprising:

a plurality of analysis regions comprising binding partners adapted to bind multiple blood markers, the multiple blood markers comprising total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), intact prostate-specific antigen (iPSA), and human kallikrein 2 (hK2), the plurality of analysis regions comprising:

a first analysis region comprising a first binding partner adapted to bind tPSA,

a second analysis region comprising a second binding partner adapted to bind fPSA,

a third analysis region comprising a third binding partner adapted to bind iPSA, and

a fourth analysis region comprising a fourth binding partner adapted to bind hK2;

multiple detection devices configured to detect presence of analytes in the plurality of analysis regions, wherein the multiple detection devices are configured to detect, using luminescent detection, emissions from the plurality of analysis regions indicative of the analytes bound to their respective binding partners, and wherein each of the analytes is selected from a group consisting of tPSA, fPSA, iPSA, and hK2,

the method comprising:

using a computer to perform:

obtaining a value for an age of a person associated with a sample;

receiving, from the multiple detection devices, values for tPSA and one or more of fPSA, iPSA, and hK2;

processing the value for the age and the value for tPSA to determine a probability of a positive biopsy for prostate cancer, wherein processing the value for the age and the value for tPSA comprises:

determining which logistic regression model of a plurality of logistic regression models to use for determining the probability of a positive biopsy for prostate cancer based on the value for tPSA received from the multiple detection devices, wherein determining which logistic regression model to use comprises:

selecting a first logistic regression model from the plurality of logistic regression models when the value of tPSA is below a threshold, the first logistic regression model comprising a first plurality of predictive variables corresponding to tPSA and one or more of fPSA, iPSA, and hK2, respectively; and

selecting a second logistic regression model from the plurality of logistic regression models when the value of tPSA is above the threshold, the second logistic regression model comprising a second plurality of predictive variables including a predictive variable corresponding to tPSA, wherein the first plurality of predictive variables is different from the second plurality of predictive variables;

after selecting the first logistic regression model or the second logistic regression model:

determining whether the selected logistic regression model includes a variable corresponding to each of the multiple blood markers;

when it is determined that the selected logistic regression model includes a variable corresponding to each of the multiple blood markers, evaluating the selected logistic regression model by scaling values of variables corresponding to the age and each of the multiple blood markers by their respective coefficient values to produce respective scaled values and summing the respective scaled values to determine a first logit; and

when it is determined that the selected logistic regression model does not include a variable corresponding to each of the multiple blood markers, evaluating the selected logistic regression model by scaling values of variables corresponding to the age and tPSA by their respective coefficient values to produce respective scaled values and summing the respective scaled values to determine a second logit; and

determining the probability of a positive biopsy for prostate cancer using the first logit or the second logit; and

outputting an indication of the determined probability of a positive biopsy for prostate cancer; and

performing a biopsy on the person associated with the sample based on the indication of the determined probability of a positive biopsy for prostate cancer.