US 2019/0160189 A1 · PREDICTING PEPTIDE RECEPTOR RADIOTHERAPY USING A GENE EXPRESSION ASSAY

Abstract

The present invention is directed to methods for providing a peptide receptor radiotherapy treatment recommendation for a subject having a neuroendocrine tumor by determining the expression level of each of at least 9 biomarkers comprising ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, and ALG9. In some embodiments, the methods can further include determining the expression level of each of NAP1L1, NOL3, and TECPR2.

Claims52

Dependent claims

A method of providing a peptide receptor radiotherapy (PRRT) treatment recommendation for a subject having a neuroendocrine tumor (NET), the method comprising:

determining the expression level of at least 9 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 9 biomarkers, wherein the 9 biomarkers comprise ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, and ALG9;
normalizing the expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3 to the expression level of ALG9, thereby obtaining a normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3;
summing the normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3, thereby obtaining a summated expression level;
determining a first score, wherein the first score is 1 when the summated expression level is equal to or greater than a first predetermined cutoff value, or the first score is 0 when the summated expression level is below the first predetermined cutoff value;
determining a second score based on the histological grade of the NET, wherein the second score is 1 when the NET is designated high grade, or the second score is 0 when the NET is designated low grade;
calculating a third score based on the following equation:
Third Score=39.22787−40.80341*(First Score)−18.441*(Second Score);
and
providing a recommendation that the NET will respond to PRRT when the third score is equal to or less than a second predetermined cutoff value, or
providing a recommendation that the NET will not respond to PRRT when the third score is above the second predetermined cutoff value.

7 more elements

A method of providing a peptide receptor radiotherapy (PRRT) treatment recommendation for a subject having a neuroendocrine tumor (NET), the method comprising:

determining the expression level of at least 12 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 12 biomarkers, wherein the 12 biomarkers comprise ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, TECPR2, and ALG9;
normalizing the expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, and TECPR2 to the expression level of ALG9, thereby obtaining a normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, and TECPR2;
summing the normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2 PLD3, NAP1L1, NOL3, and TECPR2, thereby obtaining a summated expression level;
determining a first score, wherein the first score is 1 when the summated expression level is equal to or greater than a first predetermined cutoff value, or the first score is 0 when the summated expression level is below the first predetermined cutoff value;
determining a second score based on the histological grade of the NET, wherein the second score is 1 when the NET is designated high grade, or the second score is 0 when the NET is designated low grade;
calculating a third score based on the following equation:
Third Score=39.22787−40.80341*(First Score)−18.441*(Second Score);
and
providing a recommendation that the NET will respond to PRRT when the third score is equal to or less than a second predetermined cutoff value, or
providing a recommendation that the NET will not respond to PRRT when the third score is above the second predetermined cutoff value.

7 more elements

A method of treating a subject with peptide receptor radiotherapy (PRRT), wherein the subject has a neuroendocrine tumor (NET), the method comprising:

determining the expression level of at least 9 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 9 biomarkers, wherein the 9 biomarkers comprise ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, and ALG9;
normalizing the expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3 to the expression level of ALG9, thereby obtaining a normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3;
summing the normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3, thereby obtaining a summated expression level;
determining a first score, wherein the first score is 1 when the summated expression level is equal to or greater than a first predetermined cutoff value, or the first score is 0 when the summated expression level is below the first predetermined cutoff value;
determining a second score based on the histological grade of the NET, wherein the second score is 1 when the NET is designated high grade, or the second score is 0 when the NET is designated low grade;
calculating a third score based on the following equation:
Third Score=39.22787−40.80341*(First Score)−18.441*(Second Score);
and
administering PRRT to the subject when the third score is equal to or greater than the predetermined cutoff value.

6 more elements

A method of treating a subject with peptide receptor radiotherapy (PRRT), wherein the subject has a neuroendocrine tumor (NET), the method comprising:

determining the expression level of at least 12 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 12 biomarkers, wherein the 12 biomarkers comprise ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, TECPR2, and ALG9;
normalizing the expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, and TECPR2 to the expression level of ALG9, thereby obtaining a normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, and TECPR2;
summing the normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2 PLD3, NAP1L1, NOL3, and TECPR2, thereby obtaining a summated expression level;
determining a first score, wherein the first score is 1 when the summated expression level is equal to or greater than a first predetermined cutoff value, or the first score is 0 when the summated expression level is below the first predetermined cutoff value;
determining a second score based on the histological grade of the NET, wherein the second score is 1 when the NET is designated high grade, or the second score is 0 when the NET is designated low grade;
calculating a third score based on the following equation:
Third Score=39.22787−40.80341*(First Score)−18.441*(Second Score);
and
administering PRRT to the subject when the third score is equal to or greater than the predetermined cutoff value.

6 more elements

Dependencies are inferred from the claim text.

Facts

Application

16/203,803Filed 29 Nov 2018

Priority

30 Nov 2017

Published

30 May 2019

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

A61K 51/088
Peptides, e.g. proteins , carriers being peptides, polyamino acids, proteins: conjugates with carriers being peptides, polyamino acids or proteins
A61P 35/00
Antineoplastic agents
C12Q 1/6806
Involving nucleic acids: preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6837
Enzymatic or biochemical coupling of nucleic acids to a solid phase: using probe arrays or probe chips

Abstract

Claims52

Dependent claims

A method of providing a peptide receptor radiotherapy (PRRT) treatment recommendation for a subject having a neuroendocrine tumor (NET), the method comprising:

determining the expression level of at least 9 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 9 biomarkers, wherein the 9 biomarkers comprise ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, and ALG9;
normalizing the expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3 to the expression level of ALG9, thereby obtaining a normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3;
summing the normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3, thereby obtaining a summated expression level;
determining a first score, wherein the first score is 1 when the summated expression level is equal to or greater than a first predetermined cutoff value, or the first score is 0 when the summated expression level is below the first predetermined cutoff value;
determining a second score based on the histological grade of the NET, wherein the second score is 1 when the NET is designated high grade, or the second score is 0 when the NET is designated low grade;
calculating a third score based on the following equation:
Third Score=39.22787−40.80341*(First Score)−18.441*(Second Score);
and
providing a recommendation that the NET will respond to PRRT when the third score is equal to or less than a second predetermined cutoff value, or
providing a recommendation that the NET will not respond to PRRT when the third score is above the second predetermined cutoff value.

7 more elements

A method of providing a peptide receptor radiotherapy (PRRT) treatment recommendation for a subject having a neuroendocrine tumor (NET), the method comprising:

determining the expression level of at least 12 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 12 biomarkers, wherein the 12 biomarkers comprise ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, TECPR2, and ALG9;
normalizing the expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, and TECPR2 to the expression level of ALG9, thereby obtaining a normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, and TECPR2;
summing the normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2 PLD3, NAP1L1, NOL3, and TECPR2, thereby obtaining a summated expression level;
determining a first score, wherein the first score is 1 when the summated expression level is equal to or greater than a first predetermined cutoff value, or the first score is 0 when the summated expression level is below the first predetermined cutoff value;
determining a second score based on the histological grade of the NET, wherein the second score is 1 when the NET is designated high grade, or the second score is 0 when the NET is designated low grade;
calculating a third score based on the following equation:
Third Score=39.22787−40.80341*(First Score)−18.441*(Second Score);
and
providing a recommendation that the NET will respond to PRRT when the third score is equal to or less than a second predetermined cutoff value, or
providing a recommendation that the NET will not respond to PRRT when the third score is above the second predetermined cutoff value.

7 more elements

A method of treating a subject with peptide receptor radiotherapy (PRRT), wherein the subject has a neuroendocrine tumor (NET), the method comprising:

determining the expression level of at least 9 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 9 biomarkers, wherein the 9 biomarkers comprise ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, and ALG9;
normalizing the expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3 to the expression level of ALG9, thereby obtaining a normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3;
summing the normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, and PLD3, thereby obtaining a summated expression level;
determining a first score, wherein the first score is 1 when the summated expression level is equal to or greater than a first predetermined cutoff value, or the first score is 0 when the summated expression level is below the first predetermined cutoff value;
determining a second score based on the histological grade of the NET, wherein the second score is 1 when the NET is designated high grade, or the second score is 0 when the NET is designated low grade;
calculating a third score based on the following equation:
Third Score=39.22787−40.80341*(First Score)−18.441*(Second Score);
and
administering PRRT to the subject when the third score is equal to or greater than the predetermined cutoff value.

6 more elements

A method of treating a subject with peptide receptor radiotherapy (PRRT), wherein the subject has a neuroendocrine tumor (NET), the method comprising:

determining the expression level of at least 12 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 12 biomarkers, wherein the 12 biomarkers comprise ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, TECPR2, and ALG9;
normalizing the expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, and TECPR2 to the expression level of ALG9, thereby obtaining a normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2, PLD3, NAP1L1, NOL3, and TECPR2;
summing the normalized expression level of each of ARAF1, BRAF, KRAS, RAF-1, ATP6V1H, OAZ2, PANK2 PLD3, NAP1L1, NOL3, and TECPR2, thereby obtaining a summated expression level;
determining a first score, wherein the first score is 1 when the summated expression level is equal to or greater than a first predetermined cutoff value, or the first score is 0 when the summated expression level is below the first predetermined cutoff value;
determining a second score based on the histological grade of the NET, wherein the second score is 1 when the NET is designated high grade, or the second score is 0 when the NET is designated low grade;
calculating a third score based on the following equation:
Third Score=39.22787−40.80341*(First Score)−18.441*(Second Score);
and
administering PRRT to the subject when the third score is equal to or greater than the predetermined cutoff value.

6 more elements

Dependencies are inferred from the claim text.

Predicting peptide receptor radiotherapy using a gene expression assay

Life of this patent

Abstract

Claims52

Predicting peptide receptor radiotherapy using a gene expression assay

Life of this patent

Abstract

Claims52