# US 11,111,525 B2 · Methods, kits and compositions pertaining to the suppression of the detectable probe binding to randomly distributed repeat sequences genomic nucleic acid

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- Number: US 11,111,525 B2
- Document ID: US11111525B2
- Status: Granted
- Kind: B2
- Application number: 15/925,119
- Filed: 2018-03-19
- Published: 2018-11-01
- Granted: 2021-09-07
- Earliest claimed: 2001-09-24
- Assignees: Applied Biosystems, LLC; Agilent Technologies, Inc.
- Applicants: Applied Biosystems, LLC; Agilent Technologies, Inc.
- Inventors: Kirsten Vang Nielsen; Jens Hyldig-Nielsen; Brett F. Williams
- Web page: https://patentgrep.com/patent/US11111525B2

## CPC

- C12Q 1/6832: Enhancement of hybridisation reaction
- C12Q 1/6837: using probe arrays or probe chips (C12Q1/6874 takes precedence)
- C12Q 1/6876: Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q 2600/156: Polymorphic or mutational markers
- 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

This invention is directed to methods, kits, non-nucleotide probes as well as other compositions pertaining to the suppression of binding of detectable nucleic acid probes to undesired nucleotide sequences of genomic nucleic acid in assays designed to determine target genomic nucleic acid.

## Claims

### Claim 1

A method for comparing a sample of genomic nucleic acid with that of a control sample using a genomic nucleic acid reference array, said method comprising:
a) providing a sample of genomic nucleic acid to be tested;
b) providing a control of genomic nucleic acid, wherein the control and the sample are differentially labeled;
c) providing a genomic nucleic acid reference array;
d) providing a mixture of two or more non-nucleotide probes wherein one probe of the mixture comprises a nucleobase sequence that is at least ninety percent homologous to a sequence selected from the group consisting of: SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13, and another probe of the mixture comprises a nucleobase sequence selected from the group consisting of: TT(k)TTTTT(k)TTTLysOLysOTTT(k)TTTTT(k)TT and AA(k)AAAAA(k)AAALysOLysOAAA(k)AAAAA(k)AA, wherein (k) is D-lysine, Lys is L-lysine, and O is 8-amino-3,6-dioxaoctanoic acid;
e) treating the sample and control genomic nucleic acid, the array or both the sample and control genomic nucleic acid and the array with the mixture of non-nucleotide probes under suitable hybridization conditions;
f) contacting the array with the treated mixture of sample and control genomic nucleic acid under suitable hybridization conditions; and
g) comparing the intensities of the signals from the differential labels of the array to be caused by hybridization of the probes to genomic nucleic acid thereby determine one or more variations in copy numbers of sequences in the sample as compared with the relative copy numbers of substantially identical sequences in the control.

### Claim 2 (depends on 1)

The method of claim 1, wherein hybridization on the genomic array is determined using an intercalating dye that is specific for a nucleic acid/nucleic acid hybrid.

### Claim 3 (depends on 1)

The method of claim 1, wherein hybridization on the genomic array is determined using a detectable antibody, or antibody fragment, that is specific for a nucleic acid/nucleic acid hybrid.

### Claim 4 (depends on 1)

The method of claim 1, wherein the sample of genomic nucleic acid to be tested and, as appropriate, the reference sample of genomic nucleic acid are labeled with a detectable moiety such that hybridization on the genomic array is determined by determining the presence, absence, amount or location of the detectable label on said one or more genomic arrays.

### Claim 5 (depends on 1)

The method of claim 1, wherein the genomic array comprises nucleic acid that is prepared from BAC clones.

### Claim 6 (depends on 1)

The method of claim 1, wherein the nucleobases are exactly homologous to the identified sequences.

### Claim 7 (depends on 1)

The method of claim 1, wherein the mixture comprises from about 5 to about 50 non-nucleotide probes of different nucleobase sequence.

### Claim 8 (depends on 1)

The method of claim 1, wherein the mixture comprises from about 10 to about 25 non-nucleotide probes of different nucleobase sequence.