US 2024/0151727 A1 · DIAGNOSTIC ALGORITHMS FOR DETERMINING AND TREATING CLINICALLY SIGNIFICANT PROSTATE CANCER BASED ON SIALYLATED AND FUCOSYLATED PROSTATE SPECIFIC ANTIGEN

Abstract

Provided herein are an α2-3 disialylated PSA protein standard and an α2-6 disialylated PSA protein standard, as well as various methods for measuring the relative (fractional) amount of the total N-acetylneuraminic acid (Neu5Ac) that is α2-3-linked N-acetylneuraminic acid (α2-3-linked Neu5Ac) and is α2-6-linked N-acetylneuraminic acid (α2-6-linked Neu5Ac) on PSA present in a blood serum or plasma sample, which is useful for determining whether a subject has a low risk (GG1), intermediate risk (GG2) or a high risk (GG3, 4 or 5) prostate cancer and/or determining and/or treating whether a human subject suspected of having prostate cancer should receive a needle biopsy. Also included are methods of monitoring and treating a prostate cancer patient post prostate cancer removal surgery for need of additional cancer treatment.

Claims18

Dependent claims

A method for measuring the relative amounts of α2-3-linked N-acetylneuraminic acid (α2-3-linked Neu5Ac) and α2-6-linked N-acetylneuraminic acid (α2-6-linked Neu5Ac) on PSA present in a blood serum or plasma sample, the method comprising;

a) Extracting PSA from the blood serum or plasma sample using an anti-PSA antibody;
b) Performing enzymatic treatment of a first portion of the extracted PSA with an α2-3-linked Neu5Ac specific neuraminidase that specifically removes α2-3-linked Neu5Ac to obtain a first PSA extract;
c) Performing enzymatic treatment of a second portion of the extracted PSA with a non-specific neuraminidase capable of removing both α2-3- and α2-6-linked Neu5Ac to obtain a second PSA extract;
d) Measuring and quantifying the relative amount of the total Neu5Ac that is α2-3-linked Neu5Ac wherein the measuring and quantifying are performed with electrospray ionization mass spectrometry (ESI-MS) and center-of-mass (CoM) analysis of the PSA that is present in the following:
i) a portion of the extracted PSA that was not enzymatically treated with a neuraminidase;
and in
ii) the first and second PSA extracts;
and
e) Quantification of the fractional amount of α2-3-linked Neu5Ac in PSA from the CoM analysis.

6 more elements

A method of determining whether a human subject suspected of having prostate cancer should receive a needle biopsy, the method comprising:

a) Extracting PSA from the blood serum or plasma sample using an anti-PSA antibody;
b) Performing enzymatic treatment of a first portion of the extracted PSA with an α2-3-linked Neu5Ac specific neuraminidase that specifically removes α2-3-linked Neu5Ac to obtain a first PSA extract;
c) Performing enzymatic treatment of a second portion of the extracted PSA with a non-specific neuraminidase capable of removing both α2-3- and α2-6-linked Neu5Ac to obtain a second PSA extract;
d) Measuring and quantifying the relative amount of the total Neu5Ac that is α2-3-linked Neu5Ac wherein the measuring and quantifying are performed with electrospray ionization mass spectrometry (ESI-MS) and center-of-mass (CoM) analysis of the PSA that is present in the following:
i) a portion of the extracted PSA that was not enzymatically treated with a neuraminidase;
and in
ii) the first and second PSA extracts;
and
e) Quantification of the fractional amount of α2-3-linked Neu5Ac in PSA from the CoM analysis;
and
i. when the fraction (percentage) of total Neu5Ac on PSA that is α2-3-linked Neu5Ac is greater than 0.280 (28.0%) recommend the subject proceed immediately to a needle biopsy and forego the need for a diagnostic MRI scan;
and
ii. when the fraction (percentage) is less than 0.240 (24.0%) recommend no diagnostic MRI scan and no needle biopsy.

10 more elements

A method of monitoring and treating a prostate cancer patient post prostate cancer removal surgery for need of additional cancer treatment, the method comprising:

a) Extracting PSA from the blood serum or plasma sample using an anti-PSA antibody;
b) Performing enzymatic treatment of a first portion of the extracted PSA with an α2-3-linked Neu5Ac specific neuraminidase that specifically removes α2-3-linked Neu5Ac to obtain a first PSA extract;
c) Performing enzymatic treatment of a second portion of the extracted PSA with a non-specific neuraminidase capable of removing both α2-3- and α2-6-linked Neu5Ac to obtain a second PSA extract;
d) Measuring and quantifying the relative amount of the total Neu5Ac that is α2-3-linked Neu5Ac wherein the measuring and quantifying are performed with electrospray ionization mass spectrometry (ESI-MS) and center-of-mass (CoM) analysis of the PSA that is present in the following:
i) a portion of the extracted PSA that was not enzymatically treated with a neuraminidase;
and in
ii) the first and second PSA extracts;
and
e) Quantification of the fractional amount of α2-3-linked Neu5Ac in PSA from the CoM analysis;
and when the fraction (percentage) of total Neu5Ac on PSA that is α2-3-linked Neu5Ac is greater than 0.280 (28.0%) recommend or treat the prostate cancer patient with additional cancer treatment;
and when the total Neu5Ac on PSA that is α2-3-linked Neu5Ac falls between ≥0.240 (24.0%) and ≤0.280 (28.0%), perform intensified monitoring post-treatment;
and wherein when the fraction (percentage) of total Neu5Ac on PSA that is α2-3-linked Neu5Ac is less than 0.240 (24.0%), then no perform no monitoring post-treatment.

9 more elements

a) Extracting PSA from the blood serum or plasma sample using an anti-PSA antibody to obtain a PSA extraction sample;
b) Measuring and quantifying the relative amount of the total Neu5Ac that is α2-3-linked Neu5Ac wherein the measuring and quantifying are performed with electrospray ionization mass spectrometry (ESI-MS) and center-of-mass (CoM) analysis of the PSA that is present in the PSA extraction sample;
c) Performing an enzymatic treatment on the PSA extraction sample with an α2-3-linked Neu5Ac specific neuraminidase that specifically removes α2-3-linked Neu5Ac to obtain a first treated PSA extraction sample and measuring and quantifying the relative amount of the total Neu5Ac that is α2-3-linked Neu5Ac wherein the measuring and quantifying are performed with electrospray ionization mass spectrometry (ESI-MS) and center-of-mass (CoM) analysis of the PSA that is present in first treated PSA extraction sample;
d) Performing an enzymatic treatment on the first treated PSA extraction sample with a non-specific neuraminidase capable of removing both α2-3- and α2-6-linked Neu5Ac to obtain a second PSA extraction sample and measuring and quantifying the relative amount of the total Neu5Ac that is α2-3-linked Neu5Ac wherein the measuring and quantifying are performed with electrospray ionization mass spectrometry (ESI-MS) and center-of-mass (CoM) analysis of the PSA that is present in the second PSA extraction sample;
and
e) Quantification of the fractional amount of α2-3-linked Neu5Ac in PSA from the CoM analyses performed in steps b), c), and d).

3 more elements

Dependencies are inferred from the claim text.

Diagnostic algorithms for determining and treating clinically significant prostate cancer based on sialylated and fucosylated prostate specific antigen

Life of this patent

Diagnostic algorithms for determining and treating clinically significant prostate cancer based on sialylated and fucosylated prostate specific antigen

Life of this patent

Abstract

Claims18