US 12,681,023 B2Granted

Compositions and methods for diagnosing and treating chronic kidney disease

AssigneeSociete des Produits Nestle S.A.

InventorQinghong Li

Life of this patent

Estimating the term…

Abstract

The present invention relates to methods and compositions for diagnosing and enabling treatment of chronic kidney disease in a feline. In one embodiment, a method of diagnosing chronic kidney disease (CKD) in a feline can comprise measuring a normalized relative abundance or absolute quantification of a first serum biomarker and determining if the feline has CKD, early-stage CKD, or late-stage CKD based on the normalized relative abundance or absolute quantification.

Claims9

Dependent claims

A method of enabling treatment or slowing progression of chronic kidney disease in a feline, the method comprising:

(a) diagnosing chronic kidney disease (CKD) in the feline by (i) measuring a first serum biomarker, selected from the serum biomarkers listed in Tables 1 or 3 in normalized relative abundance, or selected from the serum biomarkers listed in Table 2 in absolute quantification:
TABLE 1
Diagnostic Range
(measured as normalized relative abundance)
Early-
Indeter-
Late-
Non-
Stage
minate
Stage
Serum Biomarker
CKD
CKD
Stage
CKD
4-ureidobutyrate
<−0.37
−0.37 to 0.379
0.38 to 1.5
>1.5
erythronate
<−0.49
−0.49 to 0.8
—
>0.8
6-oxopiperidine-2-
<−0.5
−0.5 to 0.469
0.47 to 1.48
>1.48
carboxylate
N-acetyl-
<−0.24
−0.24 to 0.39
0.40 to 1.2
>1.2
isoputreanine
retinol (Vitamin A)
<−0.29
−0.29 to 0.18
0.181 to 1.3
>1.3
pseudouridine
<−0.49
−0.49 to 0.61
—
>0.61
homocitrulline
<−0.19
−0.19 to 0.78
0.78 to 1.2
>1.2
ribonate
<−0.29
−0.29 to 0.53
0.531 to 0.82
>0.82
1-methylhistidine
<−0.39
−0.39 to 0.8
0.81 to 1.03
>1.03
3-hydroxy-2-
<−0.56
−0.56 to 0.164
0.165 to 1.2
>1.2
ethylpropionate
5,6-dihydrouridine
<−0.49
−0.49 to 0.8
—
>0.8
3,4-dihydroxy-
<−0.29
−0.29 to 0.4
0.41 to 1.0
>1.0
butyrate
formiminoglutamate
<−0.39
−0.39 to 0.9
—
>0.9
gamma-
<−0.29
−0.29 to 0.74
0.741 to 1.0
>1.0
carboxyglutamate
(S)-3-
<−0.219
−0.219 to 0.11
0.111 to 0.97
>0.97
hydroxybutyry-
lcarnitine
hydroxyasparagine
<−0.18
−0.18 to 0.64
0.641 to 0.83
>0.83
palmitoylcarnitine
<−0.47
−0.47 to 0.28
0.281 to 0.97
>0.97
aconitate
<−0.29
−0.29 to 0.44
0.441 to 0.88
>0.88
[cis or trans]
N1-methylinosine
<−0.29
−0.29 to 0.74
—
>0.74
orotidine
<−0.29
−0.29 to 0.6
—
>0.6
7-methylguanine
<−0.19
−0.19 to 0.54
0.541 to 0.96
>0.96
N-acetylserine
<−0.29
−0.29 to 0.7
—
>0.7
succinylcarnitine
<−0.09
−0.09 to 0.65
—
>0.65
2R,3R-
<−0.419
−0.419 to 0.43
0.431 to 0.85
>0.85
dihydroxybutyrate
2-O-methylascorbic
<−0.299
−0.299 to 0.65
0.651 to 1.07
>1.07
acid
O-sulfo-L-tyrosine
<−0.39
−0.39 to 0.6
—
>0.6
N-acetyltaurine
<−0.29
−0.29 to 0.19
0.191 to 0.98
>0.98
5-
<−0.19
−0.19 to 0.74
0.75 to 0.91
>0.91
hydroxy-
methylcytidine
arabitol/xylitol
<−0.39
−0.39 to 0.76
0.77 to 1.04
>1.04
arachidoyl carnitine
<−0.29
−0.29 to 0.34
0.341 to 0.97
>0.97
lyxonate
<−0.39
−0.39 to 0.8
—
>0.8
N6,N6-
<−0.29
−0.29 to 0.41
0.42 to 1.17
>1.17
dimethyllysine
2,3-dihydroxy-5-
<−0.29
−0.29 to 0.56
0.561 to 0.65
>0.65
methylthio-4-
pentenoate
(DMTPA)
hexanoyltaurine
<−0.32
−0.32 to 0.79
—
>0.79
allantoin
<−0.39
−0.39 to 0.79
—
>0.79
3-hydroxy-3-
<−0.29
−0.29 to 0.05
0.051 to 0.92
>0.92
methylglutarate
allantoic acid
<−0.14
−0.14 to 0.6
—
>0.6
myo-inositol
<−0.29
−0.29 to 0.67
0.68 to 0.93
>0.93
urea
<−0.444
−0.444 to 0.59
0.6 to 0.72
>0.72
dimethylglycine
<−0.39
−0.39 to 0.77
0.771 to 0.96
>0.96
TABLE 2
Diagnostic Range
(measured as absolute quantification in μg/mL)
Indeter-
Late-
Early-Stage
minate
Stage
Serum Biomarker
Non-CKD
CKD
Stage
CKD
3-Methyl-L-
<0.92
0.92 to 1.22
—
>1.22
Histidine
Acetylserine
<0.1
0.1 to 0.16
—
>0.16
Acetylthreonine
<0.08
0.08 to 0.12
—
>0.12
Beta-Pseudouridine
<1.03
1.03 to 2.12
—
>2.12
D-Arabitol
<0.27
0.27 to 0.44
—
>0.44
Meso-Erythritol
<0.48
0.48 to 0.98
—
>0.98
Myo-Inositol
<10.33
10.33 to 16.58
—
>16.58
N-Acetylalanine
<0.09
0.09 to 0.11
—
>0.11
Phenylacetyl-
<0.015
0.015 to 0.02
—
>0.02
glutamine
Tryptophan
>9.14
9.14 to 7
—
<7
Urea
<707.4
707.4 to 1150.6
—
>1150.6
TABLE 3
Diagnostic Range
(measured as normalized
relative abundance)
Early-
Indeter-
Late-
Stage
minate
Stage
Serum Biomarker
Non-CKD
CKD
Stage
CKD
1-methylguanidine
<0.73
0.73 to 1.53
—
>1.53
1-methyl-5-
<0.75
0.75 to 1.36
—
>1.36
imidazolelactate
5-(galactosylhydroxy)-
<0.82
0.82 to 1.43
—
>1.43
lysine
methionine sulfone
<0.8
0.8 to 1.47
—
>1.47
5-methylthioadenosine
<0.85
0.85 to 1.43
—
>1.43
(MTA)
N-carbamoylputrescine
<0.81
0.81 to 1.29
—
>1.29
oxindolylalanine
<0.78
0.78 to 1.34
—
>1.34
N6-carboxymethyllysine
<0.82
0.82 to 1.44
—
>1.44
ascorbic acid 2-sulfate
<0.75
0.75 to 1.45
—
>1.45
ascorbic acid 3-sulfate
<0.81
0.81 to 1.34
—
>1.34
citrate
<0.8
0.8 to 1.5
—
>1.5
carnitine
<0.87
0.87 to 1.29
—
>1.29
3-hydroxyadipate
<0.82
0.82 to 1.42
—
>1.42
azelate (C9-DC)
<0.84
0.84 to 1.3
—
>1.3
2S,3R-dihydroxybutyrate
<0.92
0.92 to 1.32
—
>1.32
glycerol 3-phosphate
<0.86
0.86 to 1.46
—
>1.46
orotate
<0.88
0.88 to 1.32
—
>1.32
3-ureidoisobutyrate
<0.91
0.91 to 1.37
—
>1.37
gamma-glutamyl-epsilon-
<0.91
0.91 to 1.43
—
>1.43
lysine
gamma-glutamylhistidine
<0.91
0.91 to 1.35
—
>1.35
gamma-glutamylisoleucine
<0.93
0.93 to 1.37
—
>1.37
2,6-dihydroxybenzoic acid
<0.93
0.93 to 1.3
—
>1.3
mannonate
<0.77
0.77 to 1.44
—
>1.44
(ii) measuring a normalized relative abundance or absolute quantification of a second serum biomarker selected from the serum biomarkers listed in Tables 1 or 3 in normalized relative abundance, or selected from the serum biomarkers listed in Table 2 in absolute quantification;
(iii) determining that the feline has CKD if the normalized relative abundance or absolute quantification have values outside the range under the non-CKD column, determining that the feline has early-stage chronic kidney disease if the normalized relative abundance or absolute quantification of the first and second serum biomarkers have values in the range under the early-stage CKD column, or determining that the feline has late-stage CKD if the normalized relative abundance or absolute quantification of the first and second serum biomarkers have values in the range under the late-stage CKD column;
and
(iv) if the first and second serum biomarkers do not fall under the same diagnosis, measuring a normalized relative abundance or absolute quantification of one or more additional biomarkers to achieve a simple majority such that a diagnosis can be made;
and
(b) feeding a composition to the feline, wherein the composition treats or slows the progression of CKD in the feline.

440 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/085,807Filed 21 Dec 2022 · us provisional application
Priority: 27 Dec 2021
Published: US 2023/0204605 A129 Jun 2023
Granted: 14 Jul 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

G01N 33/50
Biological material, e.g. blood, urine ; Haemocytometers: chemical analysis of biological material, e.g. blood, urine; Testing involving…
G01N 33/6893
Involving proteins, peptides or amino acids: related to diseases not provided for elsewhere
A23L 33/40
Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof: complete food formulations for specific consumer…
G01N 2570/00
Omics

Family

Application63/293,855Us provisional application · filed 27 Dec 2021
US 2023/0204605 A1Pre-grant publication · published 29 Jun 2023
US 12,681,023 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A method of enabling treatment or slowing progression of chronic kidney disease in a feline, the method comprising:

(a) diagnosing chronic kidney disease (CKD) in the feline by (i) measuring a first serum biomarker, selected from the serum biomarkers listed in Tables 1 or 3 in normalized relative abundance, or selected from the serum biomarkers listed in Table 2 in absolute quantification:
TABLE 1
Diagnostic Range
(measured as normalized relative abundance)
Early-
Indeter-
Late-
Non-
Stage
minate
Stage
Serum Biomarker
CKD
CKD
Stage
CKD
4-ureidobutyrate
<−0.37
−0.37 to 0.379
0.38 to 1.5
>1.5
erythronate
<−0.49
−0.49 to 0.8
—
>0.8
6-oxopiperidine-2-
<−0.5
−0.5 to 0.469
0.47 to 1.48
>1.48
carboxylate
N-acetyl-
<−0.24
−0.24 to 0.39
0.40 to 1.2
>1.2
isoputreanine
retinol (Vitamin A)
<−0.29
−0.29 to 0.18
0.181 to 1.3
>1.3
pseudouridine
<−0.49
−0.49 to 0.61
—
>0.61
homocitrulline
<−0.19
−0.19 to 0.78
0.78 to 1.2
>1.2
ribonate
<−0.29
−0.29 to 0.53
0.531 to 0.82
>0.82
1-methylhistidine
<−0.39
−0.39 to 0.8
0.81 to 1.03
>1.03
3-hydroxy-2-
<−0.56
−0.56 to 0.164
0.165 to 1.2
>1.2
ethylpropionate
5,6-dihydrouridine
<−0.49
−0.49 to 0.8
—
>0.8
3,4-dihydroxy-
<−0.29
−0.29 to 0.4
0.41 to 1.0
>1.0
butyrate
formiminoglutamate
<−0.39
−0.39 to 0.9
—
>0.9
gamma-
<−0.29
−0.29 to 0.74
0.741 to 1.0
>1.0
carboxyglutamate
(S)-3-
<−0.219
−0.219 to 0.11
0.111 to 0.97
>0.97
hydroxybutyry-
lcarnitine
hydroxyasparagine
<−0.18
−0.18 to 0.64
0.641 to 0.83
>0.83
palmitoylcarnitine
<−0.47
−0.47 to 0.28
0.281 to 0.97
>0.97
aconitate
<−0.29
−0.29 to 0.44
0.441 to 0.88
>0.88
[cis or trans]
N1-methylinosine
<−0.29
−0.29 to 0.74
—
>0.74
orotidine
<−0.29
−0.29 to 0.6
—
>0.6
7-methylguanine
<−0.19
−0.19 to 0.54
0.541 to 0.96
>0.96
N-acetylserine
<−0.29
−0.29 to 0.7
—
>0.7
succinylcarnitine
<−0.09
−0.09 to 0.65
—
>0.65
2R,3R-
<−0.419
−0.419 to 0.43
0.431 to 0.85
>0.85
dihydroxybutyrate
2-O-methylascorbic
<−0.299
−0.299 to 0.65
0.651 to 1.07
>1.07
acid
O-sulfo-L-tyrosine
<−0.39
−0.39 to 0.6
—
>0.6
N-acetyltaurine
<−0.29
−0.29 to 0.19
0.191 to 0.98
>0.98
5-
<−0.19
−0.19 to 0.74
0.75 to 0.91
>0.91
hydroxy-
methylcytidine
arabitol/xylitol
<−0.39
−0.39 to 0.76
0.77 to 1.04
>1.04
arachidoyl carnitine
<−0.29
−0.29 to 0.34
0.341 to 0.97
>0.97
lyxonate
<−0.39
−0.39 to 0.8
—
>0.8
N6,N6-
<−0.29
−0.29 to 0.41
0.42 to 1.17
>1.17
dimethyllysine
2,3-dihydroxy-5-
<−0.29
−0.29 to 0.56
0.561 to 0.65
>0.65
methylthio-4-
pentenoate
(DMTPA)
hexanoyltaurine
<−0.32
−0.32 to 0.79
—
>0.79
allantoin
<−0.39
−0.39 to 0.79
—
>0.79
3-hydroxy-3-
<−0.29
−0.29 to 0.05
0.051 to 0.92
>0.92
methylglutarate
allantoic acid
<−0.14
−0.14 to 0.6
—
>0.6
myo-inositol
<−0.29
−0.29 to 0.67
0.68 to 0.93
>0.93
urea
<−0.444
−0.444 to 0.59
0.6 to 0.72
>0.72
dimethylglycine
<−0.39
−0.39 to 0.77
0.771 to 0.96
>0.96
TABLE 2
Diagnostic Range
(measured as absolute quantification in μg/mL)
Indeter-
Late-
Early-Stage
minate
Stage
Serum Biomarker
Non-CKD
CKD
Stage
CKD
3-Methyl-L-
<0.92
0.92 to 1.22
—
>1.22
Histidine
Acetylserine
<0.1
0.1 to 0.16
—
>0.16
Acetylthreonine
<0.08
0.08 to 0.12
—
>0.12
Beta-Pseudouridine
<1.03
1.03 to 2.12
—
>2.12
D-Arabitol
<0.27
0.27 to 0.44
—
>0.44
Meso-Erythritol
<0.48
0.48 to 0.98
—
>0.98
Myo-Inositol
<10.33
10.33 to 16.58
—
>16.58
N-Acetylalanine
<0.09
0.09 to 0.11
—
>0.11
Phenylacetyl-
<0.015
0.015 to 0.02
—
>0.02
glutamine
Tryptophan
>9.14
9.14 to 7
—
<7
Urea
<707.4
707.4 to 1150.6
—
>1150.6
TABLE 3
Diagnostic Range
(measured as normalized
relative abundance)
Early-
Indeter-
Late-
Stage
minate
Stage
Serum Biomarker
Non-CKD
CKD
Stage
CKD
1-methylguanidine
<0.73
0.73 to 1.53
—
>1.53
1-methyl-5-
<0.75
0.75 to 1.36
—
>1.36
imidazolelactate
5-(galactosylhydroxy)-
<0.82
0.82 to 1.43
—
>1.43
lysine
methionine sulfone
<0.8
0.8 to 1.47
—
>1.47
5-methylthioadenosine
<0.85
0.85 to 1.43
—
>1.43
(MTA)
N-carbamoylputrescine
<0.81
0.81 to 1.29
—
>1.29
oxindolylalanine
<0.78
0.78 to 1.34
—
>1.34
N6-carboxymethyllysine
<0.82
0.82 to 1.44
—
>1.44
ascorbic acid 2-sulfate
<0.75
0.75 to 1.45
—
>1.45
ascorbic acid 3-sulfate
<0.81
0.81 to 1.34
—
>1.34
citrate
<0.8
0.8 to 1.5
—
>1.5
carnitine
<0.87
0.87 to 1.29
—
>1.29
3-hydroxyadipate
<0.82
0.82 to 1.42
—
>1.42
azelate (C9-DC)
<0.84
0.84 to 1.3
—
>1.3
2S,3R-dihydroxybutyrate
<0.92
0.92 to 1.32
—
>1.32
glycerol 3-phosphate
<0.86
0.86 to 1.46
—
>1.46
orotate
<0.88
0.88 to 1.32
—
>1.32
3-ureidoisobutyrate
<0.91
0.91 to 1.37
—
>1.37
gamma-glutamyl-epsilon-
<0.91
0.91 to 1.43
—
>1.43
lysine
gamma-glutamylhistidine
<0.91
0.91 to 1.35
—
>1.35
gamma-glutamylisoleucine
<0.93
0.93 to 1.37
—
>1.37
2,6-dihydroxybenzoic acid
<0.93
0.93 to 1.3
—
>1.3
mannonate
<0.77
0.77 to 1.44
—
>1.44
(ii) measuring a normalized relative abundance or absolute quantification of a second serum biomarker selected from the serum biomarkers listed in Tables 1 or 3 in normalized relative abundance, or selected from the serum biomarkers listed in Table 2 in absolute quantification;
(iii) determining that the feline has CKD if the normalized relative abundance or absolute quantification have values outside the range under the non-CKD column, determining that the feline has early-stage chronic kidney disease if the normalized relative abundance or absolute quantification of the first and second serum biomarkers have values in the range under the early-stage CKD column, or determining that the feline has late-stage CKD if the normalized relative abundance or absolute quantification of the first and second serum biomarkers have values in the range under the late-stage CKD column;
and
(iv) if the first and second serum biomarkers do not fall under the same diagnosis, measuring a normalized relative abundance or absolute quantification of one or more additional biomarkers to achieve a simple majority such that a diagnosis can be made;
and
(b) feeding a composition to the feline, wherein the composition treats or slows the progression of CKD in the feline.

440 more elements

Facts

Application

18/085,807Filed 21 Dec 2022 · us provisional application

Priority

27 Dec 2021

Published

US 2023/0204605 A129 Jun 2023

Granted

14 Jul 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

G01N 33/50
Biological material, e.g. blood, urine ; Haemocytometers: chemical analysis of biological material, e.g. blood, urine; Testing involving…
G01N 33/6893
Involving proteins, peptides or amino acids: related to diseases not provided for elsewhere
A23L 33/40
Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof: complete food formulations for specific consumer…
G01N 2570/00
Omics