# US 8,568,995 B2 · Methods for assessing modified LDL immune complexes in subjects having or at risk of coronary artery disease

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- Number: US 8,568,995 B2
- Document ID: US8568995B2
- Status: Granted
- Kind: B2
- Application number: 12/885,020
- Filed: 2010-09-17
- Published: 2011-05-26
- Granted: 2013-10-29
- Earliest claimed: 2009-09-18
- Assignees: MUSC Foundation for Research Development; Department of Veterans Affairs
- Applicants: Maria F. Lopes-Virella; Gabriel T. Virella
- Inventors: Maria F. Lopes-Virella; Gabriel T. Virella
- Web page: https://patentgrep.com/patent/US8568995B2

## CPC

- G01N 33/92: involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)}
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2440/38: addition of carbohydrates, e.g. glycosylation, glycation
- G01N 2800/042: Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
- G01N 2800/324: Coronary artery diseases, e.g. angina pectoris, myocardial infarction
- G01N 2800/50: Determining the risk of developing a disease
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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 the analysis of modified LDL in the context of immune complexes. In particular, ox-LDL and AGE-LDL are shown to predict the development of coronary artery disease and other micro- and macrovascular disorders, particularly in the context of diabetes.

## Claims

### Claim 1

A method of predicting risk of coronary artery disease (CAD) in a subject comprising:
(a) providing a modified low density lipoprotein-immune complex (mod-LDL-IC)-containing sample from said subject;
(b) measuring oxidized-LDL immune complexes (ox-LDL-IC) and/or advanced glycation endproduct-LDL immune complexes (AGE-LDL-IC) in said sample;
(c) comparing the amount of ox-LDL-IC and/or AGE-LDL-IC in said sample to a normal standard; and
(d) predicting that said subject is at risk of developing CAD where an elevated amount of ox-LDL-IC and/or AGE-LDL-IC as compared to said standard is observed, or predicting that said subject is at not risk of developing CAD based where an elevated amount of ox-LDL-IC and/or AGE-LDL-IC as compared to said standard is not observed.

### Claim 2 (depends on 1)

The method of claim 1, wherein said mod-LDL-IC-containing sample is serum or plasma.

### Claim 3 (depends on 1)

The method of claim 1, wherein measuring comprises (i) isolating mod-LDL-IC, (ii) separating mod-LDL from antibodies in said mod-LDL-IC, and (iii) determining ox-LDL and/or AGE-LDL from said mod-LDL-IC levels.

### Claim 4 (depends on 3)

The method of claim 3, wherein isolating mod-LDL-IC comprises precipitation.

### Claim 5 (depends on 4)

The method of claim 4, wherein separating comprises affinity chromatography of precipitated mod-LDL-IC followed by selective elution of mod-LDL.

### Claim 6 (depends on 3)

The method of claim 3, wherein determining comprises capture immunoassay, competitive immunoassay, gas chromatography, mass spectrometry, gel electrophoresis or column chromatography.

### Claim 7 (depends on 1)

The method of claim 1, wherein said subject has a family history of CAD.

### Claim 8 (depends on 1)

The method of claim 1, wherein said subject exhibits elevated ox-LDL levels.

### Claim 9 (depends on 1)

The method of claim 1, wherein said subject exhibits elevated AGE-LDL levels.

### Claim 10 (depends on 1)

The method of claim 1, wherein said subject exhibits elevated ox-LDL levels and elevated AGE-LDL levels.

### Claim 11 (depends on 1)

The method of claim 1, wherein said subject does not exhibit elevated ox-LDL levels or elevated AGE-LDL levels.

### Claim 12 (depends on 1)

The method of claim 1, wherein said subject is male.

### Claim 13 (depends on 1)

The method of claim 1, wherein said subject is female.

### Claim 14 (depends on 1)

The method of claim 1, wherein said subject is 5 years of age or less.

### Claim 15 (depends on 1)

The method of claim 1, wherein said subject is 10 years of age or less.

### Claim 16 (depends on 1)

The method of claim 1, wherein said subject is 15 years of age or less.

### Claim 17 (depends on 1)

The method of claim 1, wherein said subject is 20 years of age or less.

### Claim 18 (depends on 1)

The method of claim 1, wherein said CAD is secondary to type 1 diabetes.

### Claim 19 (depends on 1)

The method of claim 1, wherein said CAD is secondary to type 2 diabetes.

### Claim 20 (depends on 1)

The method of claim 1, wherein said CAD is secondary to a chronic autoimmune disorder.
