# US 2014/0193822 A1 · Complex sets of mirnas as non-invasive biomarkers for kidney cancer

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- Number: US 2014/0193822 A1
- Document ID: US20140193822A1
- Status: Published application
- Kind: A1
- Application number: 14/239,263
- Filed: 2012-08-03
- Published: 2014-07-10
- Earliest claimed: 2011-08-19
- Assignees: Comprehensive Biomarker Center GmbH
- Inventors: Andreas Keller; Markus Beier; Eckart Meese; Petra Leidinger; Anke Wendschlag
- Web page: https://patentgrep.com/patent/US20140193822A1

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- C12Q 2600/158: Expression markers
- C12Q 2600/178: miRNA, siRNA or ncRNA
- 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

## Abstract

The present invention relates to non-invasive methods, kits and means for diagnosing and/or prognosing of kidney cancer in a body fluid sample from a subject. Further, the present invention relates to set of polynucleotides or sets of primer pairs for detecting sets of miRNAs for diagnosing and/or prognosing of kidney cancer in a body fluid sample from a subject. In addition, the present invention relates to sets of miRNAs for diagnosing and/or prognosing of kidney cancer in a body fluid sample from a subject.

## Claims

### Claim 1

A method for diagnosing and/or prognosing of kidney cancer comprising the steps of:
(i) determining an expression profile of a set comprising at least two miRNAs representative for kidney cancer in a body fluid sample from a subject, and
(ii) comparing said expression profile to a reference, wherein the comparison of said expression profile to said reference allows for the diagnosis and/or prognosis of kidney cancer,
wherein the nucleotide sequences of the miRNAs comprised in the set are selected from the group consisting of SEQ ID NO: 1 to 465, a fragment thereof, and a sequence having at least 80% sequence identity thereto.

### Claim 2 (depends on 1)

The method of claim 1, wherein kidney cancer is a renal cell carcinoma.

### Claim 3 (depends on 1, 2)

The method of claim 1 or claim 2, wherein the body fluid sample is a blood sample, preferably a blood cell or a leukocyte containing sample or selected from whole blood, PBMC, serum, plasma, a leukocyte sample, a blood cell sample, a leukocyte-, erythrocyte- and/or a platelet-containing sample.

### Claim 4 (depends on 2, 3)

The method of claim 2 or 3, wherein the set of miRNAs comprises at least one of the sets of miRNAs listed in FIG. 2 or FIG. 9.

### Claim 5 (depends on 1, 2, 3, 4)

The method of any of the claims 1 to 4, wherein the set of miRNAs comprises at least one up-regulated miRNA listed in FIG. 7a or 7b and/or at least one down-regulated miRNA listed in FIG. 8a or 8b

### Claim 6

A set comprising polynucleotides for detecting a set comprising at least two miRNAs for diagnosing and/or prognosing of kidney cancer in a body fluid sample from a subject, wherein the nucleotide sequences of the miRNAs comprised in the set are selected from the group consisting of SEQ ID NO: 1 to 465.

### Claim 7 (depends on 6)

The set comprising polynucleotides of claim 6, wherein kidney cancer is a renal cell carcinoma.

### Claim 8 (depends on 6, 7)

The set comprising polynucleotides of claim 6 or 7, wherein the body fluid sample is a blood sample, preferably a blood cell or a leukocyte containing sample or selected from whole blood, PBMC, serum, plasma, a leukocyte sample, a blood cell sample, a leukocyte-, erythrocyte- and/or a platelet-containing sample.

### Claim 9 (depends on 6, 7, 8)

The set comprising polynucleotides of any of the claims 6 to 8, wherein the set comprising at least two miRNAs is selected from the sets of miRNAs listed in FIG. 2 or FIG. 9.

### Claim 10 (depends on 6, 7, 8, 9)

The set comprising polynucleotides of any of the claims 6 to 9, wherein the set comprising at least two miRNAs comprises at least one up-regulated miRNA listed in FIG. 7a or 7b and/or at least one down-regulated miRNA listed in FIG. 8a or 8b

### Claim 11 (depends on 6, 7, 8, 9, 10)

The set comprising polynucleotides according to any of the claims 6 to 10, wherein
(i) the polynucleotides comprised in the set are complementary to the miRNAs comprised in the set according to claim 6 or 10,
(ii) the polynucleotides comprised in the set are fragments of the polynucleotides comprised in the set according to (i), or
(iii) the polynucleotides comprised in the set have at least 80% sequence identity to the polynucleotide sequences of the polynucleotides comprised in the set according to (i) or polynucleotide fragments comprised in the set according to (ii).

### Claim 12 (depends on 6, 7, 8, 9, 10, 11)

Use of set of polynucleotides according to any of the claims 6 to 11 for diagnosing and/or prognosing kidney cancer in a subject

### Claim 13 (depends on 6, 7, 8, 9, 10, 11)

Means for diagnosing and/or prognosing of kidney cancer in a body fluid sample of a subject comprising:
(i) a set of at least two polynucleotides according to any of the claims 6 to 11 and
(ii) a biochip, a RT-PCT system, a PCR-system, a flow cytometer, a bead-based multiplex system or a next generation sequencing system.

### Claim 14 (depends on 13)

A kit for diagnosing and/or prognosing of kidney cancer comprising
(i) means for determining an expression profile of a set comprising at least two miRNAs representative for kidney cancer in a body fluid sample from a subject according to claim 13, and
(ii) at least one reference.

### Claim 15

A set of miRNAs isolated from a body fluid sample from a subject for diagnosing and/or prognosing of kidney cancer, wherein the miRNAs are selected from the group consisting of SEQ ID NO: 1 to 465

### Claim 16 (depends on 15)

The set of miRNAs of claim 15, wherein kidney cancer is a renal cell carcinoma.

### Claim 17 (depends on 15, 16)

The set of miRNAs of any of the claims 15 to 16, wherein the body fluid sample is a blood sample, preferably a blood cell or a leukocyte containing sample or selected from whole blood, PBMC, serum, plasma, a leukocyte sample, a blood cell sample, a leukocyte-, erythrocyte- and/or a platelet-containing sample.

### Claim 18 (depends on 15, 17)

The set of miRNAs of claim 15 or 17, wherein the set of miRNAs comprises at least one of the sets of miRNAs listed in FIG. 2 or FIG. 9.

### Claim 19 (depends on 15, 16, 17, 18)

The set of miRNAs of any of the claims 15 to 18, wherein the set of miRNAs comprises at least one up-regulated miRNA listed in FIG. 7a or 7b and/or at least one down-regulated miRNA listed in FIG. 8a or 8b.

### Claim 20 (depends on 15, 16, 17, 18, 19)

Use of a set of miRNAs according to any of the claims 15 to 19 for diagnosing and/or prognosing of kidney cancer in a subject.
