# US 10,301,615 B2 · Genes expressed in mental illness and mood disorders

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- Number: US 10,301,615 B2
- Document ID: US10301615B2
- Status: Granted
- Kind: B2
- Application number: 14/763,706
- Filed: 2014-01-30
- Published: 2016-01-07
- Granted: 2019-05-28
- Earliest claimed: 2013-03-01
- Assignees: PsychNostics, LLC
- Applicants: Psychnostics, LLC
- Inventors: Alagu P. Thiruvengadam; Krish Chandrasekaran
- Web page: https://patentgrep.com/patent/US10301615B2

## CPC

- C12N 15/1034: {Isolating an individual clone by screening libraries}
- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12Q 2600/136: Screening for pharmacological compounds
- C12Q 2600/158: Expression markers
- C40B 30/04: by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
- C40B 40/06: Libraries containing nucleotides or polynucleotides, or derivatives thereof
- 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
- C40B: COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES (in silico combinatorial libraries of nucleic acids, proteins or peptides G16B35/00; in silico combinatorial chemistry G16C20/60)

## Abstract

The present invention relates to a composition comprising a plurality of cDNA molecules for use in methods of detecting changes in expression of genes encoding proteins that are associated with mental illnesses and which are differentially expressed in patients with mental illnesses, such as bipolar I disorder, bipolar II disorder, unipolar disorder, schizophrenia, attention deficit hyperactive disorders, obsessive compulsive disorders, anxiety disorders or other related mood disorders. The composition and the cDNA molecules may be used in their entirety or in part as to diagnose, to stage, to treat, and/or to monitor the treatment of a subject with mental illness.

## Claims

### Claim 1

A composition comprising a plurality of cDNA molecules, wherein the plurality of cDNA molecules consists of two or more cDNA molecules selected from the group consisting of SEQ ID NOs:1-50, wherein one or more of SEQ ID NOs:1-50 may be substituted for by the complement of said cDNA molecule.

### Claim 2 (depends on 1)

The composition of claim 1, wherein said plurality of cDNA molecules consists of SEQ ID NOs:1-8, wherein one or more of SEQ ID NOs:1-8 may be substituted for by the complement of said cDNA molecule.

### Claim 3

A composition comprising a plurality of cDNA molecules, wherein the plurality of cDNA molecules consists of SEQ ID NOs:1-15, wherein one or more of SEQ ID NOs:1-15 may be substituted for by the complement of said cDNA molecule.

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

The composition of claim 1 or 3, wherein the cDNA molecules are immobilized on a substrate.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the substrate is selected from the group consisting of a nylon membrane, a nitrocellulose membrane, a polypropylene support, a glass support and a silicon support.

### Claim 6

An array comprising a plurality of cDNA molecules immobilized on a substrate, wherein the plurality of cDNA molecules consists of two or more cDNA molecules selected from the group consisting of SEQ ID NOs:1-50, wherein one or more of SEQ ID NOs:1-50 may be substituted for by the complement of said cDNA molecule.

### Claim 7 (depends on 6)

The array of claim 6, wherein said plurality of cDNA molecules consists of SEQ ID NOs:1-8, wherein one or more of SEQ ID NOs:1-8 may be substituted for by the complement of said cDNA molecule.

### Claim 8

An array comprising a plurality of cDNA molecules immobilized on a substrate, wherein the plurality of cDNA molecules consists of SEQ ID NOs:1-15, wherein one or more of SEQ ID NOs:1-15 may be substituted for by the complement of said cDNA molecule.

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

The array of claim 6 or 8, wherein the substrate is selected from the group consisting of a nylon membrane, a nitrocellulose membrane, a polypropylene support, a glass support and a silicon support.

### Claim 10 (depends on 6)

A high throughput method for detecting differential expression of one or more cDNA molecules in a sample containing nucleic acids, the method comprising:
(a) hybridizing the array of claim 6 with nucleic acids of the sample, thereby forming one or more hybridization complexes;
(b) detecting the hybridization complexes; and
(c) comparing the hybridization complexes with those of a standard, wherein differences in the size and intensity of each hybridization complex indicates differential expression of cDNAs in the sample.

### Claim 11 (depends on 10)

The method of claim 10, wherein the sample is blood or is obtained by separation from blood.

### Claim 12 (depends on 10)

The method of claim 10 wherein the nucleic acids are amplified prior to hybridization.

### Claim 13 (depends on 1)

A high throughput method of screening a library of molecules or compounds to identify a ligand which specifically binds a cDNA molecule, the method comprising:
(a) combining the composition of claim 1 with the library of molecules or compounds under conditions to allow specific binding; and
(b) detecting specific binding between each cDNA molecule and at least one molecule or compound, thereby identifying a ligand that specifically binds to each cDNA molecule.

### Claim 14 (depends on 13)

The method of claim 13 wherein the library is selected from the group consisting of DNA molecules, RNA molecules, mimetics, peptides, peptide nucleic acids, proteins, and transcription factors.

### Claim 15 (depends on 8)

A high throughput method for detecting differential expression of one or more cDNA molecules in a sample containing nucleic acids, the method comprising:
(a) hybridizing the array of claim 8 with nucleic acids of the sample, thereby forming one or more hybridization complexes;
(b) detecting the hybridization complexes; and
(c) comparing the hybridization complexes with those of a standard, wherein differences in the size and intensity of each hybridization complex indicates differential expression of cDNAs in the sample.

### Claim 16 (depends on 15)

The method of claim 15 wherein the nucleic acids are amplified prior to hybridization.

### Claim 17 (depends on 15)

The method of claim 15, wherein the sample is blood or is obtained by separation from blood.

### Claim 18 (depends on 3)

A high throughput method of screening a library of molecules or compounds to identify a ligand which specifically binds a cDNA molecule, the method comprising:
(a) combining the composition of claim 3 with the library of molecules or compounds under conditions to allow specific binding; and
(b) detecting specific binding between each cDNA molecule and at least one molecule or compound, thereby identifying a ligand that specifically binds to each cDNA molecule.

### Claim 19 (depends on 18)

The method of claim 18 wherein the library is selected from the group consisting of DNA molecules, RNA molecules, mimetics, peptides, peptide nucleic acids, proteins, and transcription factors.

### Claim 20 (depends on 1)

A high throughput method for detecting differential expression of two or more cDNA molecules in a sample containing nucleic acids, the method comprising:
(a) combining the composition of claim 1 with nucleic acids of the sample, forming one or more hybridization complexes; and
(b) detecting the hybridization complexes; and
(c) comparing the hybridization complexes with those of a standard, wherein differences in the size and intensity of each hybridization complex indicates differential expression of cDNAs in the sample.

### Claim 21 (depends on 20)

The high throughput method of claim 20, wherein the two or more cDNA molecules are differentially expressed in a sample from a subject with a mental illness in comparison with a standard from a subject without a mental illness.

### Claim 22 (depends on 21)

The high throughput method of claim 21, wherein said differential expression is a downregulation of at least two-fold in said sample from said subject with a mental illness.

### Claim 23 (depends on 21)

The high throughput method of claim 21, wherein the mental illnesses is selected from the group consisting of bipolar I disorder, bipolar II disorder, unipolar disorder, schizophrenia, an attention deficit hyperactive disorder, an obsessive compulsive disorder, an anxiety disorder and a mood related disorder.
