# US 9,752,150 B2 · Targeting chromatin modifiers for the treatment of medical conditions

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- Number: US 9,752,150 B2
- Document ID: US9752150B2
- Status: Granted
- Kind: B2
- Application number: 14/768,864
- Filed: 2014-03-14
- Published: 2016-02-18
- Granted: 2017-09-05
- Earliest claimed: 2013-03-15
- Assignees: The Board of Trustees of the Leland Stanford Junior University
- Applicants: The Board of Trustees of the Leland Stanford Junior University
- Inventors: Michael F. Clarke; Maddalena Adorno
- Web page: https://patentgrep.com/patent/US9752150B2

## CPC

- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 17/00: Drugs for dermatological disorders
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12Q 1/6883: for diseases caused by alterations of genetic material
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 31/711: Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
- A61K 31/7115: Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
- A61K 31/712: Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
- A61K 31/7125: Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/531: Stem-loop; Hairpin
- C12N 2320/30: Special therapeutic applications
- C12N 2330/51: Specially adapted vectors
- C12Q 2600/136: Screening for pharmacological compounds
- C12Q 2600/158: Expression markers
- C12Q 2600/178: miRNA, siRNA or ncRNA
- C12Y 301/02015: Ubiquitin thiolesterase (3.1.2.15)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12Y: ENZYMES

## Abstract

Methods and compositions are provided for the treatment of medical conditions associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal. Aspects of the methods include inhibiting H2A deubiquitinating enzyme activity in cells, e.g. by administering an effective amount of an H2A deubiquitinating enzyme antagonist. Also provided are screens to identify therapeutics for the treatment of medical conditions associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal.

## Claims

### Claim 1

A method of treating a medical condition associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal, the method comprising:
administering an effective amount of an antagonist of H2A deubiquitinating enzyme USP16 to the individual, wherein the antagonist reduces the amount of USP16 in a cell or binds directly to USP16.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the antagonist is a nucleic acid.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the antagonist binds directly to USP16.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the antagonist reduces the amount of USP16 protein in the cell.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the antagonist is a USP16-specific nucleic acid inhibitor.

### Claim 6 (depends on 1)

The method according to claim 1, further comprising administering an antioxidant.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the condition is a neurodevelopmental disorder; traumatic brain injury; neurodegenerative diseases; aging-associated disorder; condition associated with muscle atrophy; disease requiring the regeneration of pancreatic cells; disease requiring liver regeneration; or a condition requiring skin regeneration.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the condition is a neurodevelopmental disorder, traumatic brain injury, or neurodegenerative disease, and the treatment comprises an improvement in cognitive function.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the improvement in cognitive function comprises an improvement in memory.

### Claim 10 (depends on 9)

The method according to claim 9, further comprising measuring memory before administering the agent and after administering the agent, wherein memory after administering the agent is improved relative to memory before administering the agent.

### Claim 11 (depends on 7)

The method according to claim 7, wherein the neurodevelopmental disorder is Down's Syndrome, fragile-X syndrome, or autism.

### Claim 12 (depends on 7)

The method according to claim 7, wherein the neurodegenerative disease is Alzheimer's Disease, Parkinson's disease, or ALS.

### Claim 13 (depends on 12)

The method according to claim 12, wherein the Alzheimer's Disease is associated with Down's Syndrome.

### Claim 14 (depends on 12)

The method according to claim 12 wherein the Alzheimer's Disease is associated with traumatic brain injury.
