# US 6,893,829 B2 · Human leukocyte 12-lipoxygenase and its role in the pathogenesis of disease states

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- Number: US 6,893,829 B2
- Document ID: US6893829B2
- Status: Granted
- Kind: B2
- Application number: 09/739,843
- Filed: 2000-12-20
- Published: 2001-07-26
- Granted: 2005-05-17
- Earliest claimed: 1992-08-28
- Assignees: City of Hope
- Inventors: Jerry L. Nadler; Rama Natarajan
- Web page: https://patentgrep.com/patent/US6893829B2

## CPC

- A61K 31/045: Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 31/05: Phenols {(cannabinoids A61K31/658)}
- A61K 31/155: Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- A61K 31/195: having an amino group
- A61K 31/20: having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K 31/35: having six-membered rings with one oxygen as the only ring hetero atom
- A61K 31/352: condensed with carbocyclic rings, e.g. methantheline {(cannabinoids A61K31/658)}
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
- C12N 9/0069: {acting on single donors with incorporation of molecular oxygen, i.e. oxygenases (1.13)}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12Q 1/26: involving oxidoreductase
- C12Y 113/11012: Linoleate 13S-lipoxygenase (1.13.11.12)
- C12Y 113/11031: Arachidonate 12-lipoxygenase (1.13.11.31), i.e. lipoxygenase-type-12
- G01N 33/573: for enzymes or isoenzymes
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2333/90241: acting on single donors with incorporation of molecular oxygen, i.e. oxygenases (1.13)
- G01N 2800/042: Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Y: ENZYMES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to a method for inhibiting the etiology of disease in patients having a disease state caused by an excess of 12-lipoxygenase or its products. In particular, the invention provides for administration of a human leukocyte 12-lipoxygenase pathway inhibitor to inhibit disease etiology, to inhibit the proliferation of breast cancer and to increase insulin receptor phosphorylation in a patient having Type II diabetics.

## Claims

### Claim 1

A method for diagnosing a disease state in a patient in which 12-lipoxygenase, distinct from that found in human platelets and distinct from human 15-lipoxygenase, is an etiological agent, which comprises:
(i) obtaining a physiological specimen from said patient; and
(ii) determining whether said 12-lipoxygenase is present in said specimen at an elevated level;
wherein the presence of said 12-lipoxygenase at an elevated level indicates said disease state.

### Claim 2 (depends on 1)

The method of claim 1 in which said disease state is selected from the group consisting of an inflammatory condition, an autoimmune condition, atherosclerosis, cancer growth, cancer metastasis, dysfunctional secretion of insulin in non-insulin dependent diabetics, glucose-induced oxidative stress and the development of end-organ dysfunction or damage.

### Claim 3 (depends on 2)

The method of claim 2, wherein said disease state is atherosclerotic vascular disease, human breast cancer, or Type II diabetes.

### Claim 4 (depends on 1)

The method of claim 1 wherein said physiological specimen is selected from the group consisting of vascular smooth muscle cells, adrenal cells, aortic endothelial cells, arterial endothelial cells, monocytes, pancreas tissue, breast tissue, renal tissue, or a tumor.

### Claim 5

A method of diagnosing a disease state in a patient in which 12-HETE or 12-lipoxygenase is an etiological agent, which comprises:
(i) obtaining a physiological specimen from said patient; and
(ii) determining whether said etiological agent is present in said specimen at an elevated level;
wherein said 12-lipoxygenase is distinct from that found in human platelets and distinct form human 15-lipoxygenase, wherein the presence of said etiological agent at an elevated level indicates said disease state and wherein the disease state is selected from the group consisting of atherosclerosis, cancer growth and cancer metastasis.

### Claim 6 (depends on 5)

The method of claim 5, wherein said disease state is selected from the group consisting of atherosclerotic vascular disease and human breast cancer.

### Claim 7 (depends on 5)

The method of claim 5, wherein said physiological specimen is selected from the group consisting of vascular smooth muscle cells, adrenal cells, aortic endothelial cells, arterial endothelial cells, monocytes, breast tissue, renal tissue and a tumor.