# US 12,179,035 B2 · Phototherapeutic light for treatment of pathogens

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- Number: US 12,179,035 B2
- Document ID: US12179035B2
- Status: Granted
- Kind: B2
- Application number: 17/148,108
- Filed: 2021-01-13
- Published: 2021-05-06
- Granted: 2024-12-31
- Earliest claimed: 2015-07-28
- Assignees: KNOW Bio, LLC
- Applicants: KNOW Bio, LLC
- Inventors: Nathan Stasko; David T. Emerson; Adam Cockrell; F. Neal Hunter; Michael John Bergmann; Rebecca McDonald; Nicholas William Medendorp, Jr.; Gerald H. Negley; Katelyn P. Reighard
- Web page: https://patentgrep.com/patent/US12179035B2

## CPC

- A61N 5/0613: {Apparatus adapted for a specific treatment}
- A61N 5/0601: {Apparatus for use inside the body}
- A61N 5/0603: {for treatment of body cavities}
- A61N 5/0624: {for eliminating microbes, germs, bacteria on or in the body}
- H10H 29/10: Integrated devices comprising at least one light-emitting semiconductor component covered by group H10H20/00 (active-matrix LED displays H10H29/30)
- A61N 2005/0606: {Mouth}
- A61N 2005/0609: {Stomach and/or esophagus}
- A61N 2005/0611: {Vagina}
- A61N 2005/0626: {Monitoring, verifying, controlling systems and methods}
- A61N 2005/0643: {Applicators, probes irradiating specific body areas in close proximity}
- A61N 2005/0647: {the applicator adapted to be worn on the head}
- A61N 2005/0652: {Arrays of diodes}
- A61N 2005/0653: {Organic light emitting diodes}
- A61N 2005/0659: {infrared}
- A61N 2005/0661: {ultraviolet}
- A61N 2005/0662: {Visible light}
- A61N 2005/0663: {Coloured light}
- A61N 2005/0666: {for redirecting light to the treatment area}
- 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)
- H10H: INORGANIC LIGHT-EMITTING SEMICONDUCTOR DEVICES HAVING POTENTIAL BARRIERS

## Abstract

Methods and related devices for impinging light on tissue, for example within a body of a patient, to induce various biological effects are disclosed. Biological effects may include at least one of inactivating and/or inhibiting growth of one or more pathogens, upregulating a local immune response, stimulating enzymatic generation of nitric oxide to increase endogenous stores of nitric oxide, releasing nitric oxide from endogenous stores of nitric oxide, and inducing an anti-inflammatory effect. Wavelengths of light are selected based on intended biological effects for one or more of targeted tissue types and targeted pathogens. Light treatments may provide multiple pathogenic biological effects, either with light of a single wavelength or with light having multiple wavelengths. Devices and methods for light treatments are disclosed that provide light doses for inducing biological effects on various targeted pathogens and targeted tissues with increased efficacy and reduced cytotoxicity.

## Claims

### Claim 1

A method comprising:
providing a first dose of light to mammalian tissue that induces a first biological effect for a first pathogen, the first dose of light being administered during a first time window, and an intensity of light of the first dose decreases to a reduced non-zero value during the first time window; and
providing a second dose of light to the mammalian tissue that induces a second biological effect, the second dose of light being administered during a second time window that is different than the first time window, wherein the second time window overlaps with a portion of the first time window, and wherein the first dose differs from the second dose by at least one of the following:
the first dose comprises a first peak wavelength in a range from 400 nanometers (nm) to 490 nm, the second dose comprises a second peak wavelength in a range from 500 nm to 900 nm or in a range from 320 nm to 400 nm, and the first peak wavelength is different than the second peak wavelength; or
the first dose comprises a first radiant flux in a range from 5 milliwatts per square centimeter (mW/cm2) to 10 mW/cm2, the second dose comprises a second radiant flux in a range from 10 mW/cm2 to 60 mW/cm2, and the second dose is different than the first dose.

### Claim 2 (depends on 1)

The method of claim 1, wherein the first biological effect comprises at least one of inactivating the first pathogen in a cell-free environment, inhibiting replication of the first pathogen in a cell-associated environment, upregulating a local immune response in the mammalian tissue, stimulating enzymatic generation of nitric oxide to increase endogenous stores of nitric oxide in the mammalian tissue, releasing nitric oxide from endogenous stores of nitric oxide in the mammalian tissue, and inducing an anti-inflammatory effect in the mammalian tissue.

### Claim 3 (depends on 1)

The method of claim 1, wherein the second biological effect comprises at least one of inactivating a second pathogen in a cell-free environment, inhibiting replication of the second pathogen in a cell-associated environment, upregulating a local immune response in the mammalian tissue, stimulating enzymatic generation of nitric oxide to increase endogenous stores of nitric oxide in the mammalian tissue, releasing nitric oxide from endogenous stores of nitric oxide in the mammalian tissue, and inducing an anti-inflammatory effect in the mammalian tissue.

### Claim 4 (depends on 2)

The method of claim 2, wherein the first biological effect comprises inactivating the first pathogen that is in a cell-free environment and inhibiting replication of the first pathogen that is in a cell-associated environment.

### Claim 5 (depends on 4)

The method of claim 4, wherein the first biological effect further comprises upregulating a local immune response.

### Claim 6 (depends on 1)

The method of claim 1, wherein the first pathogen comprises at least one of a virus, a bacteria, and a fungus.

### Claim 7 (depends on 1)

The method of claim 1, wherein the first pathogen comprises at least one of coronaviridae and orthomyxoviridae.

### Claim 8 (depends on 1)

The method of claim 1, wherein:
the first dose of light is administered with a first light therapeutic index of greater than or equal to 2, the first light therapeutic index being defined as a dose concentration of the first dose that reduces viability of the mammalian tissue by 25% divided by a dose concentration of the first dose that reduces cellular percentage of the first pathogen by 50%; and
the second dose of light is administered with a second light therapeutic index of greater than or equal to 2, the second light therapeutic index being defined as a dose concentration of the second dose that reduces viability of the mammalian tissue by 25% divided by a dose concentration of the second dose that reduces cellular percentage of a second pathogen by 50%.

### Claim 9 (depends on 8)

The method of claim 8, wherein the first light therapeutic index and the second light therapeutic index are both in a range from 2 to 250.

### Claim 10 (depends on 1)

The method of claim 1, wherein the second peak wavelength is in a range from 500 nm to 900 nm.

### Claim 11 (depends on 1)

The method of claim 1, wherein the second peak wavelength is in a range from 320 nm to 400 nm.

### Claim 12 (depends on 1)

The method of claim 1, wherein the first peak wavelength in a range from 410 nm to 440 nm.

### Claim 13 (depends on 1)

The method of claim 1, wherein each of the first dose of light and the second dose of light are in a range from 0.5 joules per square centimeter (J/cm2) to 100 J/cm2.

### Claim 14 (depends on 1)

The method of claim 1, wherein providing the first dose of light comprises providing light with an irradiance to the mammalian tissue that is in a range from 5 milliwatts per square centimeter (mW/cm2) to 200 mW/cm2 over the first time window in a range from 10 seconds to 1 hour.

### Claim 15 (depends on 14)

The method of claim 14, wherein the irradiance is delivered in a continuous manner.

### Claim 16 (depends on 14)

The method of claim 14, wherein the irradiance is delivered in a plurality of discrete pulses.

### Claim 17 (depends on 16)

The method of claim 16, wherein the plurality of discrete pulses comprises a plurality of equal pulses that is delivered during the first time window.

### Claim 18 (depends on 16)

The method of claim 16, wherein the plurality of discrete pulses comprises a plurality of dissimilar pulses that is delivered during the first time window.

### Claim 19 (depends on 1)

The method of claim 1, wherein the first dose of light and the second dose of light are repeatably administered to provide a cumulative dose in a range from 1 J/cm2 to 1000 J/cm2.

### Claim 20 (depends on 1)

The method of claim 1, wherein the first dose of light and the second dose of light are provided by at least one of a light-emitting diode, an organic light-emitting diode, and a laser.

### Claim 21 (depends on 1)

The method of claim 1, wherein the first radiant flux of the first dose of light decreases during the first time window to provide the reduced non-zero value.

### Claim 22 (depends on 21)

The method of claim 21, wherein the second radiant flux of the second dose of light increases during the second time window.
