US2017137886A1PendingUtilityA1
Physiogenomic method for predicting drug metabolism reserve for antidepressants and stimulants
Est. expiryOct 26, 2029(~3.2 yrs left)· nominal 20-yr term from priority
Inventors:Gualberto RuanoDavid Victor VillagraMohan Ranjit Kumar KocherlaAndreas WindemuthJohn W. Goethe
C12Q 2600/106C12Q 2600/156G06F 19/3431C12Q 2600/172C12Q 1/6883G16B 20/10G16B 20/20G16H 50/30G16B 20/00
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Claims
Abstract
Disclosed herein are compositions and methods relevant to a novel Drug Metabolism Reserve Physiotype to determine the metabolic capacity of a human individual. The Drug Metabolism Reserve Physiotype allows the determination of the innate metabolic capacity of the patient relevant to antidepressant and stimulant treatment and can be predicted and diagnosed simply from a blood sample. In the disclosed method, an individual is genotyped for a plurality of polymorphisms in a gene encoding CYP2C9, a gene encoding CYP2C19 and a gene encoding CYP2D6, and the genotypes are used to produce four novel indices, which relate to the metabolic capacity of the human individual.
Claims
exact text as granted — not AI-modified1 . A method of treating a human psychiatric patient, the method comprising
genotyping the human psychiatric patient to produce a combinatorial genotype for the human psychiatric patient, wherein the combinatorial genotype is produced using allele specific primer extension with primers that detect all of the polymorphisms in CYP2C9, CYP2C19 and CYP2D6 according to Table 1 and detecting both alleles of the human psychiatric patient for all of the polymorphisms in CYP2C9, CYP2C19 and CYP2D6 according to Table 1, wherein the alleles detected comprise the polymorphisms in CYP2C9, CYP2C19 and CYP2D6 according to Table 1;
TABLE 1
Gene
Allele
Nucleotide Change
CYP2C9
*1
None
*2
430C > T
*3
1075A > C
*4
1076T > C
*5
1080C > G
*6
818delA
CYP2C19
*1
None
*2
681G > A
*3
636G > A
*4
1A > G
*5
1297C > T
*6
395G > A
*7
IVS5 + 2T > A
*8
358T > C
CYP2D6
*1
None
*1XN
Gene copy number (N)
*2
1661G > C
*2a
-1584C > G
*2XN
Gene copy number (N)
*3
2549delA
*4
1846G > A
*4XN
Gene copy number (N)
*5
Gene deletion
*6
1707delT
*7
2935A > C
*8
1758G > T
*9
2615 2617delAAG
*10
100C > T
*11
883G > C
*12
124G > A
*14
1758G > A
*15
137_138InsT
*17
1023C > T
*41
2988G > A
calculating one or more index scores of a Drug Metabolism Reserve Physiotype selected from the group consisting of a metabolic reserve index score, a metabolic alteration index score, an allele alteration index score and a gene alteration index score, based on Table 2, wherein the metabolic reserve index is scored 0, 0.5, 1.5 or 2.0, the metabolic alteration index is scored 0, 0.5 or 1.0, the allele alteration index is scored 0 or 1 for each copy of each allele individually according to Table 2, and the gene alteration index is scored 0 or 1 based on the combination of alleles according to Table 2, and all scores are added to produce, respectively, the metabolic reserve index score, the metabolic alteration index score, the allele alteration index score and/or the gene alteration index score; and
TABLE 2
CYP2C9
CYP2C19
CYP2D6
(SEQ ID
(SEQ ID
(SEQ ID
Metabolic
Metabolic
Allele
NO: 1)
NO: 2)
NO: 3)
Reserve
Alteration
Alteration
*1
*1
*1, *2
1.0
0
0
*2
*9, *10,
0.5
0.5
1
*17, *41
*2a
1.5
0.5
1
*1XN,
2.0
1.0
1
*2XN
*3, *4, *5,
*2, *3, *4,
*3, *4, *6,
0
1.0
1
*6
*5, *6, *7,
*7, *8, *11,
*8
*12, *14,
*15, *5,
*4XN
Gene
CYP2C9
CYP2C19
CYP2D6
Alteration
*1*1
*1*1
*1*1, *1*2,
0
*2*2
All other
All other
All other
1
allele
allele
allele
combina-
combina-
combina-
tions
tions
tions
comparing the one or more index scores for the human psychiatric patient to the distribution of the same index scores for the human population to determine the index score of the psychiatric patient relative to the population.
2 . The method of claim 1 , further comprising administering a drug regimen to the patient based upon the index score of the psychiatric patient relative to the population.
3 . The method of claim 1 , wherein the patient has been diagnosed with depression.
4 . The method of claim 3 , wherein the patient is a patient with major depressive disorder.
5 . The method of claim 4 , wherein the patient with major depressive disorder has been hospitalized for the major depressive disorder.
6 . The method of claim 1 , further comprising correlating the one or more index scores for the individual with a predicted length of hospitalization.
7 . The method of claim 1 , further comprising customizing a drug regimen for the patient to reduce a length of hospitalization or reduce a risk of re-hospitalization.
8 . The method of claim 1 , wherein the index score is for the allele alteration index.
9 . The method of claim 8 , wherein the allele alteration index score is greater than or equal to 3 and the individual is diagnosed with Drug Sensitivity Syndrome.
10 . The method of claim 1 , wherein the antidepressant or stimulant is a substrate of CYP2C9, CYP2C19 or CYP2D6.
11 . The method of claim 1 , wherein the population is a control population of non-psychiatrically ill patients or a psychiatric patient population.
12 . A method of determining if a human psychiatric patient has Drug Sensitivity Syndrome, the method comprising
genotyping the human psychiatric patient to produce a combinatorial genotype for the human psychiatric patient, wherein the combinatorial genotype is produced using allele specific primer extension with primers that detect all of the polymorphisms in CYP2C9, CYP2C19 and CYP2D6 according to Table 1 and detecting both alleles of the human psychiatric patient for all of the polymorphisms in CYP2C9, CYP2C19 and CYP2D6 according to Table 1, wherein the alleles detected comprise the polymorphisms in CYP2C9, CYP2C19 and CYP2D6 according to Table 1:
TABLE 1
Gene
Allele
Nucleotide Change
CYP2C9
*1
None
*2
430C > T
*3
1075A > C
*4
1076T > C
*5
1080C > G
*6
818delA
CYP2C19
*1
None
*2
681G > A
*3
636G > A
*4
1A > G
*5
1297C > T
*6
395G > A
*7
IVS5 + 2T > A
*8
358T > C
CYP2D6
*1
None
*1XN
Gene copy number (N)
*2
1661G > C
*2a
−1584C > G
*2XN
Gene copy number (N)
*3
2549delA
*4
1846G > A
*4XN
Gene copy number (N)
*5
Gene deletion
*6
1707delT
*7
2935A > C
*8
1758G > T
*9
2615 2617delAAG
*10
100C > T
*11
883G > C
*12
124G > A
*14
1758G > A
*15
137_138InsT
*17
1023C > T
*41
2988G > A
calculating the gene alteration index score wherein the gene alteration is scored by assigning 1 or 2 for each gene according to Table 2, and all scores are added to produce the gene alteration index score of the human psychiatric patient; and
TABLE 2
Gene
CYP2C9
CYP2C19
CYP2D6
Alteration
*1*1
*1*1
*1*1, *1*2, *2*2
0
All other allele
All other allele
All other allele
1
combinations
combinations
combinations
wherein the gene alteration index score is equal to 3 and the individual is diagnosed with Drug Sensitivity Syndrome.
13 . The method of claim 12 , further comprising, and administering a drug regimen to the patient based upon the index score of the psychiatric patient relative to the population.
14 . The method of claim 12 , wherein the patient has been diagnosed with depression.
15 . The method of claim 14 , wherein the patient is a patient with major depressive disorder.
16 . The method of claim 15 , wherein the patient with major depressive disorder has been hospitalized for the major depressive disorder.Join the waitlist — get patent alerts
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