# US 2014/0194318 A1 · Biomarkers for diagnosing alzheimer's disease

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- Number: US 2014/0194318 A1
- Document ID: US20140194318A1
- Status: Published application
- Kind: A1
- Application number: 14/217,716
- Filed: 2014-03-18
- Published: 2014-07-10
- Earliest claimed: 2002-08-23
- Assignees: Bayer Intellectual Property GmbH
- Applicants: Bayer Intellectual Property GmbH
- Inventors: Õzkan Yalkinoglu; Gerhard König; Denis F. Hochstrasser; Jean-Charles Sanchez; Odile Carrette
- Web page: https://patentgrep.com/patent/US20140194318A1

## CPC

- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/70539: {MHC-molecules, e.g. HLA-molecules}
- C07K 14/805: Haemoglobins; Myoglobins
- C07K 14/8139: {Cysteine protease (E.C. 3.4.22) inhibitors, e.g. cystatin}
- G01N 2800/2821: Alzheimer
- 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)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

A method for assessing the state of Alzheimer's disease in patients is disclosed. A method for monitoring the progression of Alzheimer's disease in patients is also disclosed. The method applies detection of specific peptide markers, e.g., using mass spectrometric analysis.

## Claims

### Claim 1

(canceled)

### Claim 2

An isolated polypeptide having the amino acid sequence of SEQ ID NO: 17.

### Claim 3

A method for assessing the state of Alzheimer's disease in a subject, wherein the method comprises detecting in a sample from the subject at least one polypeptide from each of the following groups:
a) a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16;
b) a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NO: 3, 4, 5, and 6; and
c) a polypeptide having the amino acid sequence of SEQ ID NO: 17.

### Claim 4 (depends on 3)

The method of claim 3, wherein the method further comprises contacting the sample with an antibody that specifically binds one of the polypeptides.

### Claim 5 (depends on 3)

The method of claim 3, wherein at least one polypeptide is detected by SELDI-TOF MS.

### Claim 6 (depends on 3)

The method of claim 3, wherein the method is performed on at least two samples from the subject.

### Claim 7 (depends on 3)

The method of claim 3, wherein the sample is CSF, blood, serum, plasma, urine, seminal plasma, nipple fluid, or cell extract.

### Claim 8 (depends on 3)

The method of claim 3, wherein the polypeptides are detected in one sample from the subject.

### Claim 9

A method for assessing the state of Alzheimer's disease in a subject, wherein the method comprises detecting in a sample from the subject at least three distinct polypeptides, wherein a first polypeptide is selected from the group consisting of SEQ ID NO: 3, 4, 5, 6, 7 and 17;
and wherein a second polypeptide and a third polypeptide are selected from the group consisting of:
a) a polypeptide having the amino acid sequence selected from the group consisting SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17;
b) a human cystatin C;
c) a human beta-2-microglobulin;
d) a 7.7 kD homologue of human myoglobin;
e) neurosecretory protein VGF;
f) a fragment of at least 5 amino acids of human cystatin C;
g) a fragment of at least 5 amino acids of human beta-2-microglobulin;
h) a fragment of at least 5 amino acids of the 7.7 kD homologue of human myoglobin; and
i) a fragment of at least 5 amino acids of neurosecretory protein VGF.

### Claim 10 (depends on 9)

The method of claim 9, wherein the method further comprises contacting the sample with an antibody that specifically binds one of the polypeptides.

### Claim 11 (depends on 9)

The method of claim 9, wherein at least one polypeptide is detected by SELDI-TOF MS.

### Claim 12 (depends on 9)

The method of claim 9, wherein the method is performed on at least two samples from the subject.

### Claim 13 (depends on 9)

The method of claim 9, wherein the sample is CSF, blood, serum, plasma, urine, seminal plasma, nipple fluid, or cell extract.

### Claim 14 (depends on 9)

The method of claim 9, wherein the polypeptides are detected in one sample from the subject.

### Claim 15 (depends on 9)

The method of claim 9, wherein the method comprises detecting at least four distinct polypeptides, wherein a fourth polypeptide is selected from the group consisting of:
a) a polypeptide having the amino acid sequence selected from the group consisting SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17;
b) a human cystatin C;
c) a human beta-2-microglobulin;
d) a 7.7 kD homologue of human myoglobin;
e) neurosecretory protein VGF;
f) a fragment of at least 5 amino acids of human cystatin C;
g) a fragment of at least 5 amino acids of human beta-2-microglobulin;
h) a fragment of at least 5 amino acids of the 7.7 kD homologue of human myoglobin; and
i) a fragment of at least 5 amino acids of neurosecretory protein VGF.

### Claim 16 (depends on 15)

The method of claim 15, wherein the polypeptides are detected in one sample from the subject.

### Claim 17 (depends on 15)

The method of claim 15, wherein the method comprises detecting at least five distinct polypeptides, wherein a fifth polypeptide is selected from the group consisting of:
a) a polypeptide having the amino acid sequence selected from the group consisting SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17;
b) a human cystatin C;
c) a human beta-2-microglobulin;
d) a 7.7 kD homologue of human myoglobin;
e) neurosecretory protein VGF;
f) a fragment of at least 5 amino acids of human cystatin C;
g) a fragment of at least 5 amino acids of human beta-2-microglobulin;
h) a fragment of at least 5 amino acids of the 7.7 kD homologue of human myoglobin; and
i) a fragment of at least 5 amino acids of neurosecretory protein VGF.

### Claim 18 (depends on 17)

The method of claim 17, wherein the polypeptides are detected in one sample from the subject.
