# US 2013/0156762 A1 · Mechanically-Activated Cation Channels

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- Number: US 2013/0156762 A1
- Document ID: US20130156762A1
- Status: Published application
- Kind: A1
- Application number: 13/818,609
- Filed: 2011-08-23
- Published: 2013-06-20
- Earliest claimed: 2010-08-23
- Assignees: The Scripps Research Institute; Irm LLC
- Inventors: Bertrand Coste; Ardem Patapoutian
- Web page: https://patentgrep.com/patent/US20130156762A1

## CPC

- C07K 16/18: against material from animals or humans
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- C07H 21/00: Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels}
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C12N 15/1138: {against receptors or cell surface proteins}
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- G01N 2500/04: Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Methods of screening for agents that modulate the activity of a mechanically-activated cation channel are provided. Also provided are compositions and methods for ameliorating pain by antagonizing or inhibiting mechanically-activated cation channels.

## Claims

### Claim at position 1

1-45. (canceled)

### Claim 46

A method of ameliorating pain in a subject, the method comprising administering to the subject a) an antibody that antagonizes the activity of a mechanically activated cation channel polypeptide of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:18, or SEQ ID NO:20, or b) an antisense oligonucleotide or small interfering RNA (siRNA) complementary to at least 15 contiguous nucleotides of SEQ ID NOs 1, 3, 17, or 19 wherein the antisense oligonucleotide or siRNA inhibits production of the mechanically activated cation channel polypeptide.

### Claim 47 (depends on 1)

The method of claim 1, wherein the polypeptide comprises SEQ ID NO:4 or SEQ ID NO:20.

### Claim 48 (depends on 1)

The method of claim 1 wherein the polypeptide is expressed in bladder, colon, kidney, lung, or skin.

### Claim 49 (depends on 1)

The method of claim 1, wherein the polypeptide is expressed in a dorsal root ganglion neuron.

### Claim 50 (depends on 1)

The method of claim 1, wherein the subject is a mammal.

### Claim 51 (depends on 1)

The method of claim 1, wherein the subject is a human.

### Claim 52 (depends on 1)

The method of claim 1, wherein the pain is selected from the group consisting of acute mechanical pain, chronic mechanical pain, mechanical hyperalgesia, mechanical allodynia, arthritis, inflammation, dental pain, cancer pain, and labor pain.

### Claim 53 (depends on 1)

The method of claim 1, wherein the antibody is a monoclonal antibody, a humanized antibody or a chimeric antibody.

### Claim 54 (depends on 1)

The method of claim 1, wherein the antisense oligonucleotide or siRNA comprises any one of SEQ ID NOs 5-16.

### Claim 55

An isolated antisense oligonucleotide or small interfering RNA (siRNA) complementary to at least 15 contiguous nucleotides of SEQ ID NOs:1, 3, 17, or 19 and encodes a mechanically-activated cation channel polypeptide, wherein the antisense oligonucleotide or siRNA inhibits production of the mechanically-activated cation channel polypeptide.

### Claim 56 (depends on 10)

The isolated antisense oligonucleotide or siRNA of claim 10, wherein the antisense oligonucleotide or siRNA comprises any one of SEQ ID NOs:5-16.

### Claim 57 (depends on 10)

An expression cassette comprising a promoter operably linked to a polynucleotide comprising the antisense oligonucleotide or siRNA of claim 10.

### Claim 58 (depends on 12)

A vector comprising the expression cassette of claim 12.

### Claim 59 (depends on 13)

A cell comprising the expression cassette or expression vector of claim 13, wherein the expression cassette or expression vector is heterologous to the cell.

### Claim 60

An antibody that antagonizes the activity of a mechanically-activated cation channel selected from SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:18, or SEQ ID NO:20.

### Claim 61 (depends on 15)

The antibody of claim 15, wherein the antibody is a monoclonal antibody, a humanized antibody or a chimeric antibody.

### Claim 62

A method of screening for an agent that modulates the activity of a mechanically-activated cation channel, the method comprising:
contacting a mechanically-activated cation channel polypeptide having at least 70% amino acid sequence identity to at least one of SEQ ID NOs:2, 4, 18, or 20 with an agent; and
selecting the agent that modulates the activity of the mechanically-activated cation channel polypeptide.

### Claim 63 (depends on 17)

The method of claim 17, wherein the activity of the mechanically-activated cation channel polypeptide is determined by measuring an electrophysiological change mediated by the polypeptide comprising any of a change in membrane potential, a change in current, an influx of a cation, or a mechanically activated electrophysiological change; and wherein measuring optionally comprises any of:
i) measuring a membrane potential with a membrane potential dye,
ii) measuring an electrophysiological change with a patch-clamp assay, and
iii) measuring a mechanically activated electrophysiological change.

### Claim 64 (depends on 17)

The method of claim 17, wherein the polypeptide is expressed in a cell and the contacting comprises contacting the cell with the agent; wherein the cell optionally:
i) comprises a heterologous expression cassette comprising a promoter operably linked to a polynucleotide encoding the mechanically-activated cation channel polypeptide;
ii) is a eukaryotic cell;
iii) is a neuron; or
iv) is in an animal.

### Claim 65 (depends on 17)

The method of claim 17, wherein the polypeptide comprises SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:18, or SEQ ID NO:20.