# US 11,077,165 B2 · Use of antioxidants for gene modulation

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- Number: US 11,077,165 B2
- Document ID: US11077165B2
- Status: Granted
- Kind: B2
- Application number: 11/718,963
- Filed: 2005-11-09
- Published: 2008-03-20
- Granted: 2021-08-03
- Earliest claimed: 2004-11-09
- Assignees: Hill's Pet Nutrition, Inc.
- Applicants: Steven Curtis Zicker; Inke Paetau-Robinson; Karen Joy Wedekind
- Inventors: Steven Curtis Zicker; Inke Paetau-Robinson; Karen Joy Wedekind
- Web page: https://patentgrep.com/patent/US11077165B2

## CPC

- A61K 38/063: {Glutathione}
- A23K 20/121: containing oxygen or sulfur as hetero atom
- A23K 20/142: Amino acids; Derivatives thereof
- A23K 20/174: Vitamins
- A23K 50/40: for carnivorous animals, e.g. cats or dogs
- A61K 31/085: having an ether linkage to aromatic ring nuclear carbon
- A61K 31/355: Tocopherols, e.g. vitamin E
- A61P 17/18: Antioxidants, e.g. antiradicals (preparations for protection against sunlight A61Q17/00)
- A61P 39/06: Free radical scavengers or antioxidants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A23K: FODDER
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention provides (1) methods for modulating gene expression in senescent mammals by administering antioxidant-comprising compositions to the mammals and (2) antioxidant-comprising compositions that modulate gene expression and/or reduce the oxidative stress of such mammals.

## Claims

### Claim 1

A method of treating oxidative stress in a canine in need thereof, the method comprising:
treating the oxidative stress in the canine by administering to the canine in need thereof a pet food composition comprising:
two or more antioxidants selected from a first group consisting of vitamin E, vitamin C, lipoic acid, and L-carnitine;
one or more antioxidants selected from a second group consisting of astaxanthin, rice bran, algae, curcumin, marine oil, and yeast; and
one or more antioxidants selected from a third group consisting of coenzyme Q10, lutein, lycopene, polyphenol(s), tocotrienol(s), selenium, and green tea;
wherein a total amount of the two or more antioxidants in the first group, the one or more antioxidants in the second group, and the one or more antioxidants in the third group in the composition are sufficient to treat the oxidative stress in the canine in need thereof, and
measuring a decrease in a ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in a sample from a canine in need thereof relative to a control value for the ratio of GSH to GSSG in a sample from a normal canine or population of canines, and/or relative to a previous individual baseline value from the canine,
measuring a down-regulation or an up-regulation of one or more genes selected from the group consisting of: cytochrome P450 genes, apolipoprotein genes, genes regulating hemodynamic properties, heat shock protein genes, genes regulating DNA damage, genes regulating cell cycle pathways, pro-inflammatory genes, chromaffin secretory genes, genes regulating gene transcription, NK-kB genes, genes encoding glycolytic or mitochondrial oxidative enzymes, genes encoding ribosomal protein to indicate treatment,
wherein the ratio of GSH to GSSG is an indicator of oxidative stress,
wherein the one or more genes includes cytochrome P450 genes,
wherein measuring the down-regulation or the up-regulation of the one of more genes comprises measuring an up-regulation of the cytochrome P450 genes, and
wherein the cytochrome P450 genes are selected from the group consisting of: P450, family 2, subfamily b, polypeptide 10 (Cyp2b10); P450, family 2, subfamily c, polypeptide 70 (Cyp2c70); P450, family 2, subfamily c, polypeptide 37 (Cyp2c37); P450, family 2, subfamily a, polypeptide 12 (Cyp2a12); P450, family 2, subfamily c, polypeptide 40 (Cyp2c40); P450, family 3, subfamily a, polypeptide 11 (Cyp3a11); P450, family 3, subfamily a, polypeptide 13 (Cyp3a15); P450, family 3, subfamily a, polypeptide 16 (Cyp3a16); P450, family 3, subfamily a, polypeptide 25 (Cyp3a25); P450, family 2, subfamily a, polypeptide 4 (Cyp2a4); P450, family 4, subfamily a, polypeptide 10 (Cyp4a10), and combinations thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the canine is at least 7 years old.

### Claim 3 (depends on 1)

The method of claim 1, wherein the two or more antioxidants in the first group, the one or more antioxidants in the second group, and the one or more antioxidants in the third group are also sufficient to treat a deterioration of cognitive function in the canine, wherein the cognitive function is at least one of memory loss, memory impairment, learning impairment, disorientation, and reduction in mental alertness.

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition comprises the rice bran.

### Claim 5 (depends on 1)

The method of claim 1, wherein the composition comprises the algae.

### Claim 6 (depends on 1)

The method of claim 1, wherein the composition comprises the curcumin.

### Claim 7

A method of treating oxidative stress in a canine in need thereof, the method comprising:
treating the oxidative stress in the canine by administering to the canine in need thereof a pet food composition comprising: broccoli, rice bran, marine oil, glutamine dipeptide, methionine, selenium, algae, L-threonine, lutein, lycopene, astaxanthin, beta-carotene, curcumin, and one or more antioxidants selected from the group consisting of vitamin E, vitamin C;
measuring an up-regulation of cytochrome P450 genes to indicate treatment; and
measuring an up-regulation of apolipoprotein genes to indicate treatment.

### Claim 8 (depends on 1)

The method of claim 1, wherein the sample is a blood sample.

### Claim 9 (depends on 1)

The method of claim 1, wherein the sample is a tissue sample.

### Claim 10 (depends on 9)

The method of claim 9, wherein the tissue sample is skeletal muscle.

### Claim 11 (depends on 9)

The method of claim 9, wherein the tissue sample comprises one or more of the following: liver tissue, kidney tissue, heart tissue, cerebral cortex, and skeletal muscle.

### Claim 12 (depends on 7)

The method of claim 7, wherein the sample is a blood sample.

### Claim 13 (depends on 7)

The method of claim 7, wherein the sample is a tissue sample.

### Claim 14 (depends on 13)

The method of claim 13, wherein the tissue sample is skeletal muscle.

### Claim 15 (depends on 13)

The method of claim 13, wherein the tissue sample comprises one or more of the following: liver tissue, kidney tissue, heart tissue, cerebral cortex, and skeletal muscle.

### Claim 16 (depends on 1)

The method of claim 1, wherein the one or more genes further includes the apolipoprotein genes, and wherein measuring the down-regulation or the up-regulation of the one or more genes comprises measuring an up-regulation of the apolipoprotein genes.

### Claim 17 (depends on 16)

The method of claim 16, wherein the apolipoprotein genes are selected from the group consisting of: apolipoprotein C-II (Apoc2), apolipoprotein A-I (Apoa1), apolipoprotein A-II (Apoa2), apolipoprotein A-V (Apoa5), apolipoprotein H (Apoh), and combinations thereof.

### Claim 18 (depends on 7)

The method of claim 7, wherein the apolipoprotein genes are selected from the group consisting of: apolipoprotein C-II (Apoc2), apolipoprotein A-I (Apoa1), apolipoprotein A-II (Apoa2), apolipoprotein A-V (Apoa5), apolipoprotein H (Apoh), and combinations thereof.

### Claim 19 (depends on 18)

The method of claim 18, wherein the cytochrome P450 genes are selected from the group consisting of: P450, family 2, subfamily b, polypeptide 10 (Cyp2b10); P450, family 2, subfamily c, polypeptide 70 (Cyp2c70); P450, family 2, subfamily c, polypeptide 37 (Cyp2c37); P450, family 2, subfamily a, polypeptide 12 (Cyp2a12); P450, family 2, subfamily c, polypeptide 40 (Cyp2c40); P450, family 3, subfamily a, polypeptide 11 (Cyp3a11); P450, family 3, subfamily a, polypeptide 13 (Cyp3a15); P450, family 3, subfamily a, polypeptide 16 (Cyp3a16); P450, family 3, subfamily a, polypeptide 25 (Cyp3a25); P450, family 2, subfamily a, polypeptide 4 (Cyp2a4); P450, family 4, subfamily a, polypeptide 10 (Cyp4a10), and combinations thereof.