# US 10,307,609 B2 · Compositions and methods for controlling pain

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- Number: US 10,307,609 B2
- Document ID: US10307609B2
- Status: Granted
- Kind: B2
- Application number: 14/911,405
- Filed: 2014-08-13
- Published: 2016-07-14
- Granted: 2019-06-04
- Earliest claimed: 2013-08-14
- Assignees: The Board of Trustees of the Leland Stanford Junior University; Circuit Therapeutics, Inc.
- Applicants: The Board of Trustees of the Leland Stanford Junior University; Circuit Therapeutics, Inc.
- Inventors: Shrivats Mohan Iyer; Scott L. Delp; Kathryn L. Montgomery; Karl A. Deisseroth; Christopher Towne
- Web page: https://patentgrep.com/patent/US10307609B2

## CPC

- A61N 5/062: {Photodynamic therapy, i.e. excitation of an agent}
- A01K 67/0275: Genetically modified vertebrates, e.g. transgenic
- A01K 67/0278: Knock-in vertebrates, e.g. humanised vertebrates
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61K 41/00: Medicinal preparations obtained by treating materials with wave energy or particle radiation {; Therapies using these preparations}
- A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct}
- A61K 48/0075: {characterised by an aspect of the delivery route, e.g. oral, subcutaneous}
- A61N 5/0622: {Optical stimulation for exciting neural tissue}
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 15/8509: {for producing genetically modified animals, e.g. transgenic}
- A01K 2207/15: Humanized animals
- A01K 2217/07: Animals genetically altered by homologous recombination
- A01K 2217/072: maintaining or altering function, i.e. knock in
- A01K 2227/105: Murine
- A01K 2267/03: Animal model, e.g. for test or diseases
- A01K 2267/0393: Animal model comprising a reporter system for screening tests
- C12N 2015/8527: {for producing animal models, e.g. for tests or diseases}
- C12N 2750/14141: Use of virus, viral particle or viral elements as a vector
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present disclosure provides compositions and methods for controlling pain. The present disclosure provides methods for identifying agents that control pain.

## Claims

### Claim 1

A method for controlling pain in an individual, the method comprising:
a) administering, via direct or intrathecal administration, to the individual a recombinant expression vector comprising a nucleotide sequence encoding a hyperpolarizing opsin polypeptide, wherein the opsin polypeptide is expressed in a nociceptor in the individual; and
b) activating the opsin polypeptide with light, thereby controlling the pain in the individual.

### Claim 2 (depends on 1)

The method of claim 1, wherein the light is delivered transdermally.

### Claim 3 (depends on 1)

The method of claim 1, wherein the opsin comprises an amino acid sequence having at least about 75% amino acid sequence identity to one of SEQ ID NOs:1, 3, 4, 6, 15, and 16.

### Claim 4 (depends on 1)

The method of claim 1, wherein the pain is neuropathic pain.

### Claim 5 (depends on 1)

The method of claim 1, wherein the nociceptor is one that is normally activated by a thermal, mechanical, or chemical stimulus.

### Claim 6 (depends on 1)

The method of claim 1, wherein the nucleotide sequence is operably linked to a promoter that provides for selective expression in a neuron.

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 1)

The method of claim 1, wherein activation of the opsin provides for an at least 10% reduction in pain.

### Claim 9 (depends on 1)

The method of claim 1, wherein the light is delivered to a treatment site within the body.

### Claim 10 (depends on 1)

The method of claim 1, wherein light is delivered through a light-generating device.

### Claim 11 (depends on 10)

The method of claim 10, wherein the light-generating device is a light cuff or sleeve.

### Claim 12 (depends on 10)

The method of claim 10, wherein the light-generating device comprises a light source and one or more optical fibers that is placed on the body of the individual.

### Claim 13 (depends on 10)

The method of claim 10, wherein the light-generating device comprises a light-emitting diode.

### Claim 14 (depends on 13)

The method of claim 13, wherein the light-emitting diode can generate blue light, green light, amber light, or yellow light.

### Claim 15 (depends on 1)

The method of claim 1, wherein the opsin comprises an amino acid sequence having at least about 85% amino acid sequence identity to one of SEQ ID NOs:1, 3, 4, 6, 15, and 16.

### Claim 16 (depends on 1)

The method of claim 1, wherein the opsin comprises an amino acid sequence having at least about 95% amino acid sequence identity to one of SEQ ID NOs:1, 3, 4, 6, 15, and 16.

### Claim 17 (depends on 1)

The method of claim 1, wherein said introducing is via intrathecal administration.

### Claim 18 (depends on 1)

The method of claim 1, wherein said introducing is via intraneural administration.

### Claim 19 (depends on 1)

The method of claim 1, wherein the recombinant expression vector is a recombinant adeno associated virus (AAV) vector.

### Claim 20 (depends on 19)

The method of claim 19, wherein the recombinant AAV vector is a recombinant AAV6 or a recombinant AAV8 vector.