Granted Patent B2

US 12,656,348 · App. 17/734,211 · Granted Jun 16, 2026

Inventors: Yan Dong (Medford, MA); Andrew J. Vickers (Brooklyn, NY); Daniel Sjoberg (New York, NY); Peter T. Scardino (New York, NY); Hans Lilja (New York, NY)

Assignee: OPKO Diagnostics, LLC

G01N33/57555G16B20/00G16B25/10G16H10/40G16H50/20G16H50/30G01N2333/96433G01N2333/96455

Abstract

Claims (30)

1 . A method for determining the probability that a prostate tissue biopsy would contain detectable aggressive prostate cancer, comprising:

i) obtaining a blood sample of a subject;

ii) subjecting the blood sample of the subject to one or more immunoassays that measure levels of kallikrein markers comprising free prostate specific antigen (fPSA), intact prostate specific antigen (iPSA), total prostate specific antigen (tPSA) and human kallikrein 2 (hK2);

iii) determining the probability that a prostate tissue biopsy obtained from the subject would contain detectable aggressive prostate cancer using a logistic regression model with aggressive prostate cancer as the outcome, wherein the logistic regression model is:

Xβ=β 0 +β 1 age+β 2 tpsa+β 3 sptpsa1+β 4 sptpsa2+β 5 fpsa+β 6 spfpsa1+β 7 spfpsa2+β 8 ipsa+β 9 hK2+β 10 dre neg +β 11 dre pos +β 12 priorbx;

wherein β 0 -β 12 are weighting coefficients, age is the age of the subject when the blood is obtained, tpsa is concentration of tPSA in ng/mL, fpsa is concentration of fPSA in ng/mL, ipsa is concentration of iPSA in ng/mL, hK2 is concentration of hK2 in ng/mL, sptpsa1 is a first spline term for tPSA, sptpsa2 is a second spline term for tPSA, spfpsa1 is a first spline term for fPSA, spfpsa2 is a second spline term for fPSA, dre neg is a value of 1 if a digital rectal examination has been confirmed as negative or a value of 0 otherwise, dre pos is a value of 1 if a digital rectal examination has been confirmed as positive or a value of 0 otherwise, and priorbx is 0 if no prior negative biopsy and 1 if the subject had a prior negative biopsy;

iv) determining that the probability from step iii) is below a threshold level; and

v) repeating steps i)-iii) at least once;

wherein the probability from repeated step iii) is above the threshold level, and the method comprises obtaining a prostate tissue biopsy from the subject and analyzing the prostate tissue biopsy to further evaluate presence of aggressive prostate cancer; and

wherein the method further comprises identifying the subject as having aggressive prostate cancer based on the obtained prostate tissue biopsy and treating the identified subject, wherein treatment comprises prostatectomy or radiotherapy.

2 . The method of claim 1 , wherein step v) comprises repeating steps i)-iii) at least once within 6 months to 60 months from first performing steps i)-iii).

3 . The method of claim 1 , wherein the aggressive prostate cancer is associated with a Gleason score of 7 or more.

4 . The method of claim 1 , wherein the blood sample is obtained from the subject within 6 months to 36 months after an initial diagnosis of non-aggressive prostate cancer.

5 . The method of claim 1 further comprising repeating steps i)-iii) at least twice, wherein the interval between each set of steps i)-iii) is in a range of 6 months to 60 months.

6 . The method of claim 1 further comprising repeating steps i)-iii) at least once per year for up to five years.

7 . The method of claim 1 , wherein the subject was previously diagnosed as having non-aggressive prostate cancer.

8 . The method of claim 7 , wherein the non-aggressive prostate cancer is associated with a Gleason score of 6.

9 . The method of claim 1 , wherein the threshold level is 12.5% or less.

10 . The method of claim 1 , further comprising repeating steps i)-iii) at least five times.

11 . The method of claim 1 ,

wherein the immunoassay that measures hK2 comprises contacting PSA in the blood sample with blocking antibodies specific for PSA; contacting hK2 present in the blood sample with a capture antibody specific for hK2 under conditions in which the capture antibody binds to hK2, thereby producing a capture-antibody-hK2 complex; and detecting the capture-antibody-hK2 complex using a tracer.

12 . The method of claim 11 , wherein the blocking antibodies specific for PSA comprise a 5F7 antibody, a 5H6 antibody, and a 2E9 antibody.

13 . The method of claim 3 , wherein the subject was previously diagnosed as having non-aggressive prostate cancer.

14 . The method of claim 13 , wherein the non-aggressive prostate cancer is associated with a Gleason score of 6.

15 . The method of claim 14 , wherein the immunoassay that measures hK2 comprises contacting PSA in the blood sample with blocking antibodies specific for PSA; contacting hK2 present in the blood sample with a capture antibody specific for hK2 under conditions in which the capture antibody binds to hK2, thereby producing a capture-antibody-hK2 complex; and detecting the capture-antibody-hK2 complex using a tracer.

16 . The method of claim 15 , wherein the blocking antibodies specific for PSA comprise a 5F7 antibody, a 5H6 antibody, and a 2E9 antibody.

17 . The method of claim 16 , wherein the threshold level is 12.5% or less.

18 . The method of claim 16 , further comprising repeating steps i)-iii) at least twice, wherein the interval between each set of steps i)-iii) is in a range of 6 months to 60 months.

19 . The method of claim 16 , further comprising repeating steps i)-iii) at least five times.

20 . The method of claim 16 , wherein step v) comprises repeating steps i)-iii) at least once within 6 months to 60 months from first performing steps i)-iii).

Assignments (1)

Continuity (3)

References Cited (281)