CA2977584C

Systems and methods for enabling appetite modulation and/or improving dietary compliance using an electro-dermal patch

Abstract

A wearable device for suppressing appetite or hunger in a patient includes a microprocessor, electrical stimulator and at least one electrode configured to deliver electrical stimulation to the epidermis, through a range of 0.1mm to 10 mm or a range of 0.1 mm to 20 mm of the dermis, of a T2 frontal thoracic dermatome to a T12 frontal thoracic dermatome or meridian of the patient and/or front or back, C5 - T1 dermatome across the hand and/or arm, and/or the upper chest regions. The device includes a pad, in which the electrode is disposed, for secure placement of the device on a skin surface of a patient. The device is adapted to provide electrical stimulation as per stimulation protocols and to communicate wirelessly with a companion control device configured to monitor and record appetite patterns of the patient. The control device is also configured to monitor, record, and modify stimulation parameters of the stimulation protocols.

CA2977584C, drawing sheet 1 — Sheet 1 of 81

Term

9.4 yearsleft in the term

Expires 24 February 2036.

10 claims: 1 independent, 9 dependent

1
5 1. An electrical dermal patch configured to modulate at least one of an appetite, hunger, satiety level, or satiation level of a patient, comprising:a housing adapted to be adhered to the patient’s epi dermal layer and configured to be placed on the patient’s front thoracic dermatomes;a controller positioned within the housing;10 at least one electrode adapted to be in electrical contact with said patient’s epidermal layer;a pulse generator positioned within the housing and in electrical communication with the controller and said at least one electrode, wherein the pulse generator is configured to generate a plurality of electrical pulses, said plurality of electrical pulses being defined by a plurality of stimulation parameters, wherein said plurality of stimulation parameters are selected such that 15 at least one of the patient’s appetite, hunger, satiety level, and satiation level modulates from a first state, prior to stimulation, to a second state after stimulation;and a transceiver in electrical communication with the controller, wherein the transceiver is configured to communicate wirelessly with an external device and to receive a signal from the external device, wherein the signal is representative of at least one parameter of the plurality 20 of electrical pulses and wherein said at least one parameter is at least one of a pulse width, a pulse amplitude, a pulse frequency, a pulse shape, a stimulation session duration, a duty cycle, or a stimulation session frequency.

1,403 paragraphs in 439 sections, as filed

SYSTEMS AND METHODS FOR ENABLING APPETITE MODULATION AND/OR IMPROVING DIETARY COMPLIANCE USING AN ELECTRO-DERMAL PATCH

CROSS-REFERENCE

The present specification relies on U.S. Patent Provisional Application Number 62/120,067, entitled “Dermatome Stimulation System” and filed on February 24, 2015, for priority. The present specification also relies on U.S. Patent Provisional Application Number 62/120,082, entitled “Dermatome Stimulation Methods” and filed on February 24, 2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/133,526, entitled “Dermatome Stimulation System” and filed on March 16, 2015, for priority. The present specification also relies on U.S. Patent Provisional Application Number 62/133,530, entitled “Dermatome Stimulation Method” and filed on March 16,2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/141,328, entitled “Dermatome Stimulation System” and filed on April 1, 2015, for priority. The present specification also relies on U.S. Patent Provisional Application Number 62/141,333, entitled “Dermatome Stimulation Method” and filed on April 1,2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/161,353, entitled “Dermatome Stimulation System” and filed on May 14, 2015, for priority. The present specification also relies on U.S. Patent Provisional Application Number 62/161,362, entitled “Dermatome Stimulation Method” and filed on May 14, 2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/189,800, entitled “Dermatome Stimulation Method” and filed on July 8, 2015, for priority. The present specification also relies on U.S. Patent Provisional Application number 62/189,805, entitled “Dermatome Stimulation System” and filed on July 8,2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/237,356, entitled “Systems and Methods for Enabling Appetite Modulation Using Transcutaneous Electrical Neurostimulation” and filed on October 5,2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/240,808, entitled “Systems and Methods for Enabling Appetite Modulation Using an ElectroDermal Patch” and filed on October 13,2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/242,944, entitled “Systems and Methods for Enabling Appetite Modulation Using an ElectroDermal Patch” and filed on October 16,2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/242,957, entitled “Systems and Methods for Enabling Appetite Modulation Using an ElectroDermal Patch” and filed on October 16,2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/246,526, entitled “Systems and Methods for Enabling Appetite Modulation Using an ElectroDermal Patch” and filed on October 26,2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/247,113, entitled “Systems and Methods for Enabling Appetite Modulation Using an ElectroDennal Patch” and filed on October 27,2015, for priority.

The present specification also relies on U.S. Patent Provisional Application Number 62/248,059, entitled “Systems and Methods for Enabling Pain Management Using an ElectroDermal Patch” and filed on October 29,2015, for priority.

FIELD

The present specification relates generally to systems and methods of modulating a patient’s appetite, hunger, satiety level, satiation level, or fullness level in a user by delivering electrical stimulation to a predetermined area of the user’s anatomy in a manner that is convenient, easy to use, and amenable to increased patient compliance. More particularly, the present specification relates to electrical stimulation devices comprising low profile, wearable, disposable skin patches that are easy to self-administer, programmable and monitorable using a mobile handheld device, and programmed to stimulate a patient’s nerves from the external surface of the patient’s epidermal layer in a manner that enables appetite or hunger control, modulation or suppression, avoids nausea, dyspepsia, minimizes habituation and enables increased compliance with a dietary regimen. The present specification further relates to a low profile, wearable, disposable skin patch that is capable of integrating with, and being controlled by, a plurality of different hardware devices or software applications depending on the type,

Date Reçue/Date Received 2022-06-08

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PCT/ÜS2016/019416 extent, nature and scope of the appetite, hunger, satiety level, satiation level, or fullness level modulation desired, the nature and degree of dietary compliance required, the amount of weight loss desired and/or the need for long term weight maintenance.

PCT/ÜS2016/019416 and is configured for extended or permanent wearability. There is also a need for a patientadministered, wearable electrical neuro-stimulation device directed toward suppressing postprandial glucose levels and effectively modulating a plurality of hormones and microbiota related to gastrointestinal functionality. There is a need for an electrical neuro-stimulation device having a size, shape, and weight, and being composed of materials that effectively allow the device to be wearable. Such a device would eliminate the need for stimulation parameters requiring large power needs (which would make wearability impractical or impossible). There is also a need for an electrical neuro-stimulation device which is controllable by a companion device (such as a smartphone) and includes no visible or tactile user interface on the stimulation device itself. There is a need for an electrical neuro-stimulation device having unique electrical stimulation and footprint, based on electrode design and stimulation parameters, which would allow users to comfortably wear the device.

There is also a need for a holistic approach to managing a patient’s caloric consumption and expenditure profile. Conventional approaches focus on caloric intake but do not analyze, monitor, or otherwise gather data on the important precursor to caloric intake, namely appetite or hunger levels. There are untapped benefits to integrating data relating to the appetite, hunger and/or craving levels, active suppression or control over appetite, caloric intake, weight gain, and caloric expenditure. These and other benefits shall be described in relation to the detailed description and figures.

SUMMARY

The following embodiments and aspects thereof are described and illustrated in conjunction with systems, tools and methods, which are meant to be exemplary and illustrative, and not limiting in scope. The present application discloses numerous embodiments.

The device may be used to treat a condition including any one of obesity, excess weight, eating disorders, metabolic syndrome and diabetes. In accordance with various aspects of the present specification, the electro-dermal patch device enables treating people with BMI (Body Mass Index) of 25 or greater (overweight being 25-30, obese being 30 and above, and morbid obesity being above 35).

In some embodiments, the present specification discloses an electrical dermal patch configured to modulate at least one of an appetite, hunger, satiety level, or satiation level of a

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PCT/ÜS2016/019416 patient comprising: a housing adapted to be adhered to the patient’s epidermal layer; a controller positioned within the housing; at least one electrode adapted to be in electrical contact with said patient’s epidermal layer; and, a pulse generator positioned within the housing and in electrical communication with the controller and said at least one electrode, wherein the pulse generator is configured to generate a plurality of electrical pulses, said plurality of electrical pulses being defined by a plurality of stimulation parameters, wherein said plurality of stimulation parameters are selected such that at least one of the patient’s appetite, hunger, satiety level, and satiation level modulates from a first state, prior to stimulation, to a second state after stimulation.

Optionally, the appetite of said patient, in the first state, is greater than the appetite of said patient in the second state.

Optionally, the first state is defined by a pré-stimulation appetite profile comprising a first plurality of quantitative appetite measurements, wherein each of said first plurality of quantitative appetite measurements is determined, prior to stimulation, using a visual analog scale and is taken at different predefined times of day, wherein the second state is defined by a post-stimulation appetite profile comprising a second plurality of quantitative appetite measurements, wherein each of said second plurality of quantitative appetite measurements is determined, after stimulation, using said visual analog scale and is taken at different predefined times of day, and wherein, for a given predefined time of day, at least one of the second plurality of quantitative appetite measurements differs from at least one of the first plurality of quantitative appetite measurements by at least 5%, thereby representing a decrease in appetite of the patient.

Optionally, the first state is defined by a pre-stimulation appetite profile comprising a first plurality of quantitative appetite measurements, wherein each of said first plurality of quantitative appetite measurements is determined, prior to stimulation, using a visual analog scale and is taken at different predefined times of day, wherein said first plurality of quantitative appetite measurements collectively define a first area representative of said first state, wherein the second state is defined by a post-stimulation appetite profile comprising a second plurality of quantitative appetite measurements, wherein each of said second plurality of quantitative appetite measurements is determined, after stimulation, using said visual analog scale and is taken at different predefined times of day, wherein said second plurality of quantitative appetite measurements collectively define a second area representative of said second state, and wherein

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PCT/ÜS2016/019416 said first area differs from said second area by at least 5%, thereby representing a decrease in the appetite of the patient.

Optionally, said plurality of stimulation parameters are further selected such that a poststimulation daily caloric intake of said patient decreases relative to a pre-stimulation daily caloric intake of said patient, wherein said pre-stimulation daily caloric intake is a function of an amount of calories consumed by the patient over a first predefined period of time prior to stimulation, and wherein said post-stimulation daily caloric intake is a function of an amount of calories consumed by the patient over a second predefined period of time equal in duration to the first predefined period of time, after stimulation is initiated.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s compliance with a target daily caloric intake increases relative to the patient’s compliance with the target daily caloric intake before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s appetite decreases, over a predefined period of time, relative to the patient’s appetite before stimulation, wherein at least one of a dyspepsia level of the patient or a nausea level of the patient does not increase more than 10%, over said predefined period of time, relative to at least one of the dyspepsia level or the nausea level of the patient before stimulation, and wherein said at least one stimulation does not cause the patient to experience a pain sensation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a pre-prandial ghrelin level of the patient reduces by at least 1% relative to a pre-prandial ghrelin level of the patient before stimulation.

Optionally, said electrical dermal patch further comprises a hydrogel pad having a top surface and a bottom surface, wherein the top surface is physically attached to a base of said housing and wherein said hydrogel pad is in electrical communication with the electrode. Still optionally, said electrical dermal patch further comprises an adhesive layer positioned on the bottom surface of the hydrogel pad.

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Optionally, the pulse generator is configured to generate an electrical field, wherein the electrical field is adapted to penetrate, via the at least one electrode, a range of 0.1 mm to 25mm through the patient’s epidermal layer.

Optionally, the plurality of electrical pulses comprise a pulse width in a range of lOpsec to 100msec, a pulse amplitude in a range of ΙΟΟμΑ to 500mA, and a pulse frequency in a range of 1Hz to 10,000Hz.

Optionally, the electrical dermal patch further comprises an impedance sensor, wherein the impedance sensor is configured to generate an impedance signal and transmit said impedance signal to the controller and wherein said controller is adapted to use said impedance signal to determine whether a degree of contact of the at least one electrode to the patient’s epidermal layer meets a threshold value.

Optionally, the electrical dermal patch further comprises a transceiver in electrical communication with the controller, wherein said transceiver is configured to communicate wirelessly with an external device and to receive a signal representative of at least one parameter of the plurality of electrical pulses, said at least one parameter being the pulse width, the pulse amplitude, the pulse frequency, a pulse shape, a stimulation session duration, a duty cycle, and a stimulation session frequency.

In some embodiments, the controller may be adapted to generate a signal based on the at least one parameter of the plurality of electrical pulses and transmit said signal to the pulse generator.

In some embodiments, the pulse generator may be configured to generate a plurality of electrical pulses in accordance with said signal from the controller and based upon the at least one parameter of the plurality of electrical pulses.

In some embodiments, the controller may be configured to modify at least one parameter of the plurality of electrical pulses based upon an input from the external device, wherein the at least one parameter of the plurality of electrical pulses is the pulse width, the pulse amplitude, the pulse frequency, a pulse shape, a stimulation session duration, a duty cycle, and a stimulation session frequency.

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PCT/ÜS2016/019416 level, a value indicative of a desired change in the patient’s nausea level, a value indicative of the patient’s weight, a value indicative of a desired change in the patient’s weight, a value indicative of an amount of calories consumed by the patient, a value indicative of a desired change in an amount of calories consumed by the patient, a value indicative of an amount of calories expended by the patient, a value indicative of a desired change in an amount of calories expended by the patient, a value for the pulse width, a value for the pulse amplitude, a value for the pulse frequency, a value for a pulse shape, a value for a stimulation session duration, a value for a duty cycle, a value for a stimulation session frequency, a change in value for the pulse width, a change in value for the pulse amplitude, a change in value for the pulse frequency, a change in value for the pulse shape, a change in value for the stimulation session duration, a change in value for the duty cycle, or a change in value for the stimulation session frequency.

In some embodiments, the present specification discloses an electrical stimulation system configured to modulate at least one of a patient’s appetite, hunger, level of satiety, or level of satiation level comprising: an electrical dermal patch adapted to be adhered to the patient’s epidermal layer, wherein said electrical dermal patch comprises a controller, at least one electrode adapted to be in electrical contact with an epidermal layer of said patient, a pulse generator in electrical communication with the controller and said at least one electrode; and a transceiver in communication with at least one of said controller and pulse generator; and a plurality of programmatic instructions, stored in a non-transient computer readable memory of a device physically separate from said electrical dermal patch, wherein, when executed, said programmatic instructions acquire patient status data, generate a modulation signal based upon said patient status data, wherein said modulation signal comprises instructions for modulating at least one of a pulse width, a pulse amplitude, a pulse frequency, a pulse shape, a duty cycle, a session duration, and a session frequency, and wirelessly transmit said modulation signal from the device to the transceiver.

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PCT/ÜS2016/019416 daily caloric intake is a function of an amount of calories consumed by the patient over a first predefined period of time prior to stimulation, and wherein said post-stimulation daily caloric intake is a function of an amount of calories consumed by the patient over a second predefined period of time equal in duration to the first predefined period of time, after stimulation is initiated.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, the patient’s compliance with a target daily caloric intake increases relative to the patient’s compliance with the target daily caloric intake before stimulation.

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Optionally, the patient’s hunger in the second state is decreased relative to the patient’s hunger in the first state, wherein said first state hunger is measured using a scale at predefined times of day over a first predefined period of time, wherein said second state hunger is measured, after stimulation is initiated, using said scale at said predefined times of day over a second predefined period of time, equal in duration to the first predefined period of time, and wherein said second state hunger decreases such that it is equal to, or less than, 95% of the first state hunger.

Optionally, the patient’s satiety level in the second state is increased relative to the patient’s satiety level in the first state, wherein said first state satiety level is measured using a scale at predefined times of day over a first predefined period of time, wherein said second state satiety level is measured, after stimulation is initiated, using said scale at said predefined times of day over a second predefined period of time, equal in duration to the first predefined period of time, and wherein said second state satiety level increases such that it is equal to, or greater than, 105% of the first state satiety level.

Optionally, the patient’s satiation level in the second state is increased relative to the patient’s satiation level in the first state, wherein said first state satiation level is measured using a scale at predefined times of day over a first predefined period of time, wherein said second state satiation level is measured, after stimulation is initiated, using said scale at said predefined times of day over a second predefined period of time, equal in duration to the first predefined period of time, and wherein said second state satiation level increases such that it is equal to, or greater than, 105% of the first state satiation level.

Optionally, the patient’s fullness level in the second state is increased relative to the patient’s fullness level in the first state, wherein said first state fullness level is measured using a scale at predefined times of day over a first predefined period of time, wherein said second state fullness level is measured, after stimulation is initiated, using said scale at said predefined times of day over a second predefined period of time, equal in duration to the first predefined period of time, and wherein said second state fullness level increases such that it is equal to, or greater than, 105% of the first state fullness level.

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PCT/ÜS2016/019416 of calories consumed by the patient over a first predefined period of time prior to stimulation, and wherein said post-stimulation daily caloric intake is a function of an amount of calories consumed by the patient over a second predefined period of time equal in duration to the first predefined period of time, after stimulation is initiated.

Optionally, said plurality of stimulation parameters are further selected such that a poststimulation daily caloric intake of said patient is less than 99% of a pre-stimulation daily caloric intake of said patient, wherein said pre-stimulation daily caloric intake is a function of an amount of calories consumed by the patient over a first predefined period of time prior to stimulation, and wherein said post-stimulation daily caloric intake is a function of an amount of calories consumed by the patient over a second predefined period of time equal in duration to the first predefined period of time, after stimulation is initiated.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s daily caloric intake decreases to a range of 600 to 1600 calories.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s daily caloric intake decreases from over 2000 calories per day to under 2000 calories per day.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s daily caloric intake decreases from over 1600 calories per day to under 1600 calories per day.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, an amount of the patient’s antral motility reduces relative to the patient’s antral motility before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, an amount of the patient’s gastric motility reduces relative to the patient’s gastric motility before stimulation.

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Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a rate of the patient’s gastric emptying reduces relative to a rate of the patient’s gastric emptying before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s appetite decreases, over a predefined period of time, relative to the patient’s appetite before stimulation, wherein at least one of a dyspepsia level of the patient or a nausea level of the patient does not increase, over said predefined period of time, relative to at least one of the dyspepsia level or the nausea level of the patient before stimulation,

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PCT/ÜS2016/019416 and wherein said at least one stimulation does not cause the patient to experience a pain sensation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s hunger decreases, over a predefined period of time, relative to the patient’s hunger before stimulation, wherein at least one of a dyspepsia level of the patient or a nausea level of the patient does not increase, over said predefined period of time, relative to at least one of the dyspepsia level or the nausea level of the patient before stimulation, and wherein said at least one stimulation does not cause the patient to experience a pain sensation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s satiety level increases, over a predefined period of time, relative to the patient’s satiety level before stimulation, wherein at least one of a dyspepsia level of the patient or a nausea level of the patient does not increase, over said predefined period of time, relative to at least one of the dyspepsia level or the nausea level of the patient before stimulation, and wherein said at least one stimulation does not cause the patient to experience a pain sensation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s satiation level increases, over a predefined period of time, relative to the patient’s satiation level before stimulation, wherein at least one of a dyspepsia level of the patient or a nausea level of the patient does not increase, over said predefined period of time, relative to at least one of the dyspepsia level or the nausea level of the patient before stimulation, and wherein said at least one stimulation does not cause the patient to experience a pain sensation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s fullness level increases, over a predefined period of time, relative to the patient’s fullness level before stimulation, wherein at least one of a dyspepsia level of the patient or a nausea level of the patient does not increase, over said predefined period of time, relative to at least one of the dyspepsia level or the nausea level of the patient before stimulation, and wherein said at least one stimulation does not cause the patient to experience a pain sensation.

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Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a total body weight of the patient reduces by at least 1% relative to a total body weight of the patient before stimulation and a well-being level of the patient does not reduce more than 5% relative to a well-being level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, an excess body weight of the patient reduces by at least 3% relative to an excess body weight of the patient before stimulation and a well-being level of the patient does not reduce more than 5% relative to a well-being level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are fiirther selected such that, after at least one stimulation, a pre-prandial ghrelin level of the patient reduces by at least 3% relative to a pre-prandial ghrelin level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, exercise output of the patient increases by at least 3% relative to the exercise output of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation session, a post-stimulation ghrelin level of said patient decreases by at least 3% relative to a pre-stimulation ghrelin level of said patient, wherein said pre-stimulation ghrelin level is measured prior to stimulation and wherein said post-stimulation ghrelin level is measured more than ten weeks after said at least one stimulation session.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a glucagon-like peptide-1 level of the patient increases by at least 3% relative to a glucagon-like peptide-1 level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a leptin level of the patient increases by at least 3% relative to a leptin level of the patient before stimulation.

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Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a peptide YY level of the patient increases by at least 3% relative to a peptide YY level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a lipopolysaccharide level of the patient reduces by at least 3% relative to a lipopolysaccharide level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a motilin-related peptide level of the patient reduces by at least 3% relative to a motilin-related peptide level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a cholecystokinin level of the patient increases by at least 3% relative to a cholecystokinin level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a resting metabolic rate of the patient increases by at least 3% relative to a resting metabolic rate of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a plasma-beta endorphin level of the patient increases by at least 3% relative to a plasma-beta endorphin level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s hunger decreases, over a predefined period of time, relative to the patient’s hunger before stimulation and a nausea level of the patient does not increase by more than 10%, over said predefined period of time, relative to the nausea level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s glucose homeostasis improves by at least 3% relative to the patient’s glucose homeostasis before stimulation.

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Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, the patient’s level of hemoglobin Ale decreases by an amount equal to at least 0.3%.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a triglyceride level of the patient decreases by at least 3% relative to a triglyceride level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a total blood cholesterol level of the patient decreases by at least 3% relative to a total blood cholesterol level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a glycemia level of the patient decreases by at least 3% relative to a glycemia level of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a degree of insulin resistance of the patient improves by at least 3% relative to a degree of insulin resistance of the patient before stimulation.

Optionally, said plurality of stimulation parameters are further selected such that, after at least one stimulation, a composition of the patient’s gut microbiota modulates from a first state to a second state, wherein the first state has a first level of bacteroidetes and a first level of firmicutes, wherein the second state has a second level of bacteroidetes and a second level of firmicutes, wherein the second level of bacteroidetes is greater than the first level of bacteroidetes by at least 3%, and wherein the second level of firmicutes is less than the first level of firmicutes by at least 3%.

Optionally, a first portion of said housing is encased in a first polymer, having a first durometer value, and a second portion of said housing is encased in a second polymer, having a second durometer value, said first durometer value being higher than the second durometer value.

Optionally, said first polymer is positioned on a periphery of the housing.

Optionally, said second polymer is positioned in a center of the housing.

Optionally, said housing is covered by at least one polymer having a hardness measure of 45-65 on a subzero shore scale.

Optionally, said housing is encased in at least one polymer having a tensile modulus of 30 psi to 45 psi.

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Optionally, said electrical dermal patch has a measurement of lOpsi to 35 psi on a flexural modulus scale.

Optionally, said at least one electrode is removably attached to a surface of the housing and has a contact surface area in a range of 0.1 in2 to 10 in2.

Optionally, the electrical dermal patch further comprises a circuit substrate positioned within said housing, wherein the controller and the pulse generator are positioned on the circuit substrate and wherein the circuit substrate comprises at least one joint. Still optionally, the joint joins a first portion of the circuit substrate and a second portion of the circuit substrate such that said first portion is configured to tilt relative to said second portion at said joint when pressure is placed on the circuit substrate.

Optionally, said at least one electrode is at least partially located within the housing and has a contact surface area in a range of 0.1 in2 to 10in2.

Optionally, the electrical dermal patch further comprises a circuit board positioned within said housing, wherein the controller and the pulse generator are positioned on the circuit board and wherein the circuit board has a maximum area of 1.5 in2.

Optionally, the electrical dermal patch has a volume in a range of 0.25in3 to 0.5in3.

Optionally, the electrical dermal patch has a weight in a range of 15 grams to 80 grams.

Optionally, the electrical dermal patch is adapted to operate with a current density in a range of ΙΟμΑ/in2 to 5000m A/in2.

Optionally, the electrical dermal patch further comprises a hydrogel pad having a top surface and a bottom surface, wherein the top surface is physically attached to a base of said housing and wherein said hydrogel pad is in electrical communication with the electrode.

Optionally, the electrical dermal patch further comprises an adhesive layer positioned on the bottom surface of the hydrogel pad.

Optionally, the adhesive layer of the electrical dermal patch is adhered to the patient’s epidermal layer, the electrical dermal patch has an average minimum peel strength in a range of 1.3 to 1.7 newtons.

Optionally, the electrical dermal patch further comprises a pad having a water based absorbing polymer and a water based electrolyte, wherein the pad has a top surface and a bottom surface, and wherein the top surface is in electrical communication with the at least one electrode.

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PCT/ÜS2016/019416 determine whether a degree of contact of the at least one electrode to the patient’s epidermal layer meets a threshold value. Optionally, said threshold value is in a range of 200 to 1000 ohms.

Optionally, said at least one of the controller and pulse generator is adapted to automatically adjust the pulse amplitude based upon said impedance signal in order to maintain a constant current.

Optionally, the at least one of the controller and pulse generator is adapted to automatically adjust the pulse amplitude based upon said impedance signal within a voltage range of 0. IV to 500V.

Optionally, the electrical dermal patch further comprises an impedance sensor, wherein the impedance sensor is configured to generate an impedance signal and transmit said impedance signal to the controller and wherein said controller is adapted to use said impedance signal to determine a value indicative of at least one of an amount of body fat of the patient and a body mass index of the patient.

Optionally, the electrical dermal patch further comprises an impedance sensor, wherein the impedance sensor is configured to generate an impedance signal and transmit said impedance signal to the controller and wherein said controller is adapted to use said impedance signal to determine if the at least one electrode is in electrical contact with the patient’s epidermal layer.

Optionally, the electrical dermal patch further comprises an impedance sensor, wherein the impedance sensor is configured to generate an impedance signal and transmit said impedance signal to the controller and wherein said controller is adapted to use said impedance signal to determine if the at least one electrode is not in electrical contact with the patient’s epidermal layer.

Optionally, the electrical dermal patch further comprises an impedance sensor, wherein the impedance sensor is configured to generate an impedance signal and transmit said impedance signal to the controller and wherein said controller is adapted to use said impedance signal to modulate the pulse amplitude in order to maintain a substantially constant current.

Optionally, the electrical dermal patch further comprises an impedance sensor, wherein the impedance sensor is configured to generate an impedance signal and transmit said impedance signal to the controller and wherein said controller is adapted to use said impedance signal to determine a value indicative of a hydration state of the patient.

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Optionally, the electrical dermal patch further comprises an accelerometer configured to monitor a degree of the patient’s movement.

Optionally, the electrical dermal patch further comprises a neural sensor configured to detect a presence of neural activity and generate at least one of an indication that the electrical dermal patch is placed in a right location, an indication that die electrical dermal patch is increasing neural activity in accordance with a stimulation protocol, an indication that a neural response rate of the patient is insufficient, and an indication that a stimulation protocol needs to be modified.

Optionally, the electrical dermal patch does not comprise an on or off switch.

Optionally, the electrical dermal patch is adapted to operate in a first state and in a second state, wherein, in the first state, the electrical dermal patch has a first average current usage and wherein, in the second state, the electrical dermal patch has a second average current usage, wherein the second average current usage is at least 1 μΑ greater than the first average current usage.

Optionally, in the first state, the electrical dermal patch is not configured to generate said plurality of electrical pulses.

Optionally, in the second state, the electrical dermal patch is configured to generate said plurality of electrical pulses.

Optionally, the controller is adapted to generate a signal based on the at least one parameter of the plurality of electrical pulses and transmit said signal to the pulse generator.

Optionally, said pulse generator is configured to generate a plurality of electrical pulses in accordance with said signal from the controller.

Optionally, said pulse generator is configured to generate a plurality of electrical pulses based upon the at least one parameter of the plurality of electrical pulses.

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Optionally, the electrical dermal patch is adapted to operate in a first state and in a second state, wherein, in the first state, the electrical dermal patch has a first average current usage, wherein, in the second state, the electrical dermal patch has a second average current usage, wherein the second average current usage is at least ΙμΑ greater than the first average current usage, and wherein the electrical dermal patch is configured to switch from said first state to said second state upon receiving a signal from the external device.

Optionally, said controller is configured to modify at least one parameter of the plurality of electrical pulses based upon an input from the external device, wherein the at least one parameter of the plurality of electrical pulses is the pulse width, the pulse amplitude, the pulse frequency, a pulse shape, a stimulation session duration, a duty cycle, and a stimulation session frequency.

Optionally, said input is a value indicative of the patient’s hunger, a value indicative of a desired change in the patient’s hunger, a value indicative of the patient’s appetite, a value indicative of a desired change in the patient’s appetite, a value indicative of the patient’s nausea level, a value indicative of a desired change in the patient’s nausea level, a value indicative of the patient’s weight, a value indicative of a desired change in the patient’s weight, a value indicative of an amount of calories consumed by the patient, a value indicative of a desired change in an amount of calories consumed by the patient, a value indicative of an amount of calories expended by the patient, a value indicative of a desired change in an amount of calories expended by the patient, a value for the pulse width, a value for the pulse amplitude, a value for the pulse frequency, a value for a pulse shape, a value for a stimulation session duration, a value for a duty cycle, a value for a stimulation session frequency, a change in value for the pulse width, a change in value for the pulse amplitude, a change in value for the pulse frequency, a change in value for the pulse shape, a change in value for the stimulation session duration, a change in value for the duty cycle, or a change in value for the stimulation session frequency.

Optionally, the electrical dermal patch is adapted to operate in a first state and in a second state, wherein: in the first state, the electrical dermal patch has an average first current usage and the electrical dermal patch is not configured to generate said plurality of electrical pulses; in the second state, the electrical dermal patch has an average second current usage and the electrical dermal patch is configured to generate said plurality of electrical pulses, wherein the average second current usage is equal to the first current usage plus at least ΙμΑ; the controller is

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PCT/ÜS2016/019416 configured to automatically switch from said first state to said second state upon receiving a signal from the external device; and the controller is configured to automatically modify at least one of said pulse width, said pulse amplitude, said pulse frequency, a pulse shape, a duty cycle, a session duration, or a session frequency based upon an input of a value indicative of the patient’s hunger, a value indicative of a desired change in the patient’s hunger, a value indicative of the patient’s appetite, a value indicative of a desired change in the patient’s appetite, a value indicative of the patient’s nausea level, a value indicative of a desired change in the patient’s nausea level, a value indicative of the patient’s weight, a value indicative of a desired change in the patient’s weight, a value indicative of an amount of calories consumed by the patient, a value indicative of a desired change in an amount of calories consumed by the patient, a value indicative of an amount of calories expended by the patient, a value indicative of a desired change in an amount of calories expended by the patient, a value for the pulse width, a value for the pulse amplitude, a value for the pulse frequency, a value for a pulse shape, a value for a session duration, a value for a duty cycle, a value for a session frequency, a change in value for the pulse width, a change in value for the pulse amplitude, a change in value for the pulse frequency, a change in value for the pulse shape, a change in value for the session duration, a change in value for the duty cycle, or a change in value for the session frequency, wherein said input is wirelessly transmitted to the transceiver of the electrical stimulation device from the external device.

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PCT/ÜS2016/019416 session duration, and a session frequency, and wirelessly transmit said modulation signal from the device to the transceiver.

Optionally, the pulse generator is configured to generate a plurality of electrical pulses and a corresponding electrical field, wherein the electrical field is adapted to penetrate a range of 0.1 mm to 25mm through the patient’s epidermal layer.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that a post-stimulation daily caloric intake of said patient decreases relative to a pre-stimulation daily caloric intake of said patient, wherein said pre-stimulation daily caloric intake is a function of an amount of calories consumed by the patient over a first predefined period of time prior to stimulation, and wherein said post-stimulation daily caloric intake is a function of an amount of calories consumed by the patient over a second predefined period of time equal in duration to the first predefined period of time, after stimulation is initiated.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that a post-stimulation daily caloric intake of said patient is less than 99% of a pre-stimulation daily caloric intake of said patient, wherein said pre-stimulation daily caloric intake is a function of an amount of calories consumed by the patient over a first predefined period of time prior to stimulation, and wherein said post-stimulation daily caloric intake is a function of an amount of calories consumed by the patient over a second predefined period of time equal in duration to the first predefined period of time, after stimulation is initiated.

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Optionally, said well-being level comprises at least one of a degree of nausea being experienced by the patient and a degree of dyspepsia being experienced by the patient.

Optionally, when executed, said programmatic instructions acquire a first stimulation protocol and use said first stimulation protocol to generate the modulation signal.

Optionally, when executed, said programmatic instructions acquire a second stimulation protocol, wherein said second stimulation protocol is different from the first stimulation protocol, and, using said second stimulation protocol, generate a second modulation signal, wherein said second modulation signal comprises instructions for modulating at least one of the pulse width, the pulse amplitude, the pulse frequency, the pulse shape, the duty cycle, the session duration, and the session frequency.

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Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, an excess body weight of the patient reduces by at least 1% relative to an excess body weight of the patient before stimulation.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a total body weight of the patient reduces by at least 1 % relative to a total body weight of the patient before stimulation and a wellbeing level of the patient does not reduce more than 5% relative to a well-being level of the patient before stimulation.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a pre-prandial ghrelin level of the patient reduces by at least 1% relative to a pre-prandial ghrelin level of the patient before stimulation.

Optionally, at least one of said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a post-prandial ghrelin level of the patient reduces by at least 1% relative to a post-prandial ghrelin level of the patient before stimulation.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a glucagon-like peptide-1 level of the patient increases by at least 1% relative to a glucagon-like peptide-1 level of the patient before stimulation.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a leptin level of the patient increases by at least 1% relative to a leptin level of the patient before stimulation.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a peptide YY level of the patient increases by at least 1% relative to a peptide YY level of the patient before stimulation.

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Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a lipopolysaccharide level of the patient reduces by at least 1% relative to a lipopolysaccharide level of the patient before stimulation.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a motilin-related peptide level of the patient reduces by at least 1% relative to a motilin-related peptide level of the patient before stimulation.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a cholecystokinin level of the patient increases by at least 1% relative to a cholecystokinin level of the patient before stimulation.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a resting metabolic rate of the patient increases by at least 1% relative to a resting metabolic rate of the patient before stimulation.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a plasma-beta endoiphin level of the patient increases by at least 1% relative to a plasma-beta endorphin level of the patient before stimulation.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, the patient’s hunger decreases, over a predefined period of time, relative to the patient’s hunger before stimulation and a nausea level of the patient does not increase by more than 10%, over said predefined period of time, relative to the nausea level of the patient before stimulation.

Optionally, the electrical dermal patch further comprises a housing and wherein at least one of the controller and the pulse generator is located within the housing.

Optionally, the at least one electrode is positioned within the housing.

Optionally, the at least one electrode is removably connected to an exterior surface of the housing.

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Optionally, said housing is covered by at least one polymer having a hardness measure of 30-70 on a subzero shore scale.

Optionally, said housing is encased in at least one polymer having a tensile modulus of 15 to 55 psi.

Optionally, the electrical stimulation system further comprises a circuit board positioned within said housing, wherein the controller and the pulse generator are positioned on the circuit board and wherein the circuit board has a maximum area of 5 in2. Optionally, the circuit board comprises a dielectric laminate having no more than three layers and having a thickness no greater than 0.05 inches.

Optionally, the housing has a substantially linear profile, a width of 4 inches or less, a length of 8 inches or less, and a height of 1 inches or less.

Optionally, the electrical dermal patch has a volume in a range of 0.25 in3 to 10 in3.

Optionally, the electrical dermal patch has a weight in a range of 15 grams to 250 grams.

Optionally, the electrical dermal patch further comprises a power source.

Optionally, the power source is two stacked batteries having a voltage in a range of 1.0 V to 8.0 V.

Optionally, the electrical dermal patch has an ingress protection rating of at least IPX4.

Optionally, the electrical dermal patch further comprises an impedance sensor configured to determine an electrode integrity of the at least one electrode.

Optionally, the pulse generator is configured to generate a plurality of electrical pulses and a corresponding electrical field, wherein the electrical field is adapted to contact a portion of at least one of the patient’s C5, C6, C7, C8, Tl, T2, T3, T4, T5, T6, T7, T8, T9, T10, Til, and T12 frontal and lateral dermatomes and wherein the electrical field is not adapted to contact any portion of the patient’s C5, C6, C7, C8, Tl, T2, T3, T4, T5, T6, T7, T8, T9, T10, Til, and T12 posterior dermatomes.

Optionally, at least one of said pulse width, said pulse amplitude, and said pulse frequency are defined such that, after at least one stimulation, a fasting glucose level of the

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PCT/ÜS2016/019416 patient reduces to a level equal to or below lOOmg/dl from a level above 100mg/dl before stimulation.

In some embodiments, the present specification discloses a method of modulating at least one of a patient’s appetite, hunger, satiety level, or satiation level comprising: providing an electrical dermal patch adapted to adhere to the patient’s epidermal layer, wherein said electrical dermal patch comprises a controller, at least one electrode adapted to be in electrical contact with said patient’s epidermal layer, and a pulse generator in electrical communication with the controller and said at least one electrode; defining a plurality of stimulation parameters; and programming the pulse generator to generate a plurality of electrical pulses using said plurality of stimulation parameters, wherein said plurality of stimulation parameters are defined such that, after applying at least one stimulation to the patient’s epidermal layer, at least one of the patient’s appetite, hunger, satiety level, and satiation level is modified.

Optionally, after applying at least one stimulation to the patient’s epidermal layer, the appetite of said patient decreases relative to the appetite of said patient prior to applying at least one stimulation.

Optionally, after applying at least one stimulation to the patient’s epidermal layer, the hunger of said patient decreases relative to the hunger of said patient prior to applying at least one stimulation.

Optionally, after applying at least one stimulation to the patient’s epidermal layer, the satiety level of said patient increases relative to the satiety level of said patient prior to applying at least one stimulation.

PCT/ÜS2016/019416 second plurality of quantitative fullness measurements, wherein each of said second plurality of quantitative fullness measurements is determined, after stimulation, using said visual analog scale and is taken at different predefined times of day, wherein said second plurality of quantitative fullness measurements collectively define a second area representative of said second state, and wherein said first area differs from said second area by at least 5%, thereby representing an increase in the fullness level of the patient.

Optionally, said plurality of stimulation parameters are defined such that, after applying at least one stimulation to the patient’s epidermal layer, the patient’s appetite modulates from a first state to a second state, wherein the patient’s appetite in the second state is decreased relative to the patient’s appetite in the first state, wherein said first state appetite is measured using a scale at predefined times of day over a first predefined period of time, wherein said second state appetite is measured, after stimulation is initiated, using said scale at said predefined times of day over a second predefined period of time, equal in duration to the first predefined period of time, and wherein said second state appetite decreases such that it is equal to, or less than, 95% of the first state appetite.

Optionally, said pulse generator generates an electrical field and wherein the electrical field is adapted to penetrate, via the at least one electrode, a range of 0.1 mm to 25mm through the patient’s epidermal layer.

Optionally, said method further comprises: determining a central electrical stimulation reaction threshold for the patient; determining a spinal electrical stimulation reaction threshold for the patient; defining at least a portion of the plurality of stimulation parameters such that at least one of a pulse width, a pulse amplitude, and a pulse frequency is set above the spinal electrical stimulation reaction threshold but below the central electrical stimulation reaction

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PCT/ÜS2016/019416 threshold; and generating said plurality of electrical pulses, wherein said plurality of electrical pulses is defined by said pulse width, said pulse amplitude, and said pulse frequency.

PCT/ÜS2016/019416

PCT/ÜS2016/019416 generator in electrical communication with the controller and said at least one electrode; generating a plurality of electrical pulses having a treatment session duration and a treatment session frequency, wherein each of said plurality of electrical pulses is defined by a pulse width, a pulse amplitude, a pulse shape, a pulse frequency and wherein said pulse shape, pulse width, said pulse amplitude, and said pulse frequency are selected to enable the person to comply with the diet plan; using an application installed on an external device to acquire data over a period of time, said data including at least one of a timing of caloric consumption, an amount of caloric consumption, and a content of a caloric consumption; after said period of time, generating a signal, using said application, based upon said data; causing the signal to be transmitted to the electrical dermal patch; and generating a second plurality of electrical pulses using a plurality of stimulation parameters, said plurality of stimulation parameters being determined based upon said signal and including at least one of a second pulse width, a second pulse amplitude, a second pulse frequency, a second pulse duty cycle, a second pulse shape, a second treatment session duration, and a second treatment session frequency.

Optionally, the epidermal layer is positioned within a range of 0.1 mm to 25mm from at least one of the person’s C5, C6, C7, C8, Tl, T2, T3, T4, T5, T6, T7, T8, T9, T10, Til, and T12 dermatomes.

Optionally, if the amount of caloric consumption varies from a predefined amount, the second pulse width is greater than the pulse width.

Optionally, if the amount of caloric consumption varies from a predefined amount, the second pulse amplitude is greater than the pulse amplitude.

Optionally, if the amount of caloric consumption varies from a predefined amount, the second pulse frequency is greater than the pulse frequency.

Optionally, if the amount of caloric consumption varies from a predefined amount, the second treatment session duration is greater than the treatment session duration.

Optionally, if the amount of caloric consumption varies from a predefined amount, the second treatment session frequency is greater than the treatment session frequency.

Optionally, the content of a caloric consumption includes at least one of an amount of carbohydrates, an amount of protein, an amount of fat, an amount of sugar, an amount of vitamins, an amount of minerals, and an amount of glycemic index.

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Optionally, if at least one of the amount of carbohydrates, the amount of fat, the amount of sugar, and the amount of glycemic index varies from a predefined amount, the second pulse width is greater than the pulse width.

Optionally, if at least one of the amount of carbohydrates, the amount of fat, the amount of sugar, and the amount of glycemic index varies from a predefined amount, the second treatment session duration is greater than the treatment session duration.

Optionally, if at least one of the amount of carbohydrates, the amount of fat, the amount of sugar, and the amount of glycemic index varies from a predefined amount, the second treatment session frequency is greater than the treatinent session frequency.

In some embodiments, the present specification discloses a method of enabling a person to comply with a diet plan comprising: providing an electrical dermal patch adapted to adhere to the person’s epidermal layer, wherein said electrical dermal patch comprises a controller, at least one electrode adapted to be in electrical contact with said patient’s epidermal layer, and a pulse generator in electrical communication with the controller and said at least one electrode; using said electrical dermal patch, generating a plurality of electrical pulses at a first predefined time of day; using an application installed on a device separate from said electrical dermal patch to acquire data over a period of time, said data including at least one of a timing of caloric consumption and an amount of caloric consumption; after said period of time, generating a signal, using said application, based upon said data; causing the signal to be transmitted to the electrical dermal patch; and generating a second plurality of electrical pulses using a plurality of stimulation parameters, said plurality of stimulation parameters being determined based upon said signal and including a second predefined time of day.

Optionally, the epidermal layer is positioned within a range of 0.1 mm to 25mm from at least one of the person’s C5, C6, C7, C8, Tl, T2, T3, T4, T5, T6, T7, T8, T9, T10, Til, and T12 dermatomes.

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Optionally, if the amount of caloric consumption varies from a predefined amount, the second plurality of electrical pulses are generated at the second predefined time of day, wherein the second predefined time of day is different from the first predefined time of day and is based on the timing of caloric consumption.

Optionally, the data further includes at least one of an amount of caibohydrates consumed by the person, an amount of fat consumed by the person, and an amount of sugar consumed by the person.

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PCT/ÜS2016/019416 a puise amplitude, a pulse frequency, a pulse duty cycle, a pulse shape, a treatment session duration, and a treatment session frequency; receiving data into an application installed on a device separate from said electrical dermal patch, said data including at least one of a timing of caloric consumption, a content of caloric consumption, and an amount of caloric consumption; using the application to compare at least one of the timing of caloric consumption, the content of caloric consumption, and the amount of caloric consumption with at least one of the recommended timing of caloric consumption, recommended content of caloric consumption, and recommended amount of caloric consumption; generating a signal, using said application, based upon said comparison; causing the signal to be transmitted to the electrical dermal patch; and generating a second plurality of electrical pulses using a plurality of stimulation parameters, said plurality of stimulation parameters being determined based upon said signal and including at least one of a second pulse width, a second pulse amplitude, a second pulse frequency, a second pulse duty cycle, a second pulse shape, a second treatment session duration, a second treatment session frequency, and a second predefined time of day.

Optionally, if the amount of caloric consumption varies from the recommended amount of caloric consumption by a predefined amount, the second pulse width is greater than the pulse width.

Optionally, if the amount of caloric consumption varies from the recommended amount of caloric consumption by a predefined amount, the second pulse amplitude is greater than the pulse amplitude.

Optionally, if the amount of caloric consumption varies from the recommended amount of caloric consumption by a predefined amount, the second pulse frequency is greater than the pulse frequency.

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Optionally, if the amount of caloric consumption varies from the recommended amount of caloric consumption by a predefined amount, the second pulse width is less than the pulse width.

Optionally, if the amount of caloric consumption varies from the recommended amount of caloric consumption by a predefined amount, the second pulse amplitude is less than the pulse amplitude.

Optionally, if the amount of caloric consumption varies from the recommended amount of caloric consumption by a predefined amount, the second pulse frequency is less than the pulse frequency.

Optionally, if the amount of caloric consumption varies from the recommended amount of caloric consumption by a predefined amount, the second treatment session duration is less than the treatment session duration.

Optionally, if the amount of caloric consumption varies from the recommended amount of caloric consumption by a predefined amount, the second treatment session frequency is less than the treatment session frequency.

Optionally, the content of a caloric consumption includes at least one of an amount of carbohydrates, an amount of fat, an amount of sugar, and an amount of glycemic index.

Optionally, if at least one of the amount of carbohydrates, the amount of fat, the amount of sugar, or the amount of glycemic index varies from the recommended content of caloric consumption by a predefined amount, the second pulse width is greater than the pulse width.

Optionally, if the amount of carbohydrates, the amount of fat, the amount of sugar, or the amount of glycemic index varies from the recommended content of caloric consumption by a predefined amount, the second pulse amplitude is greater than the pulse amplitude.

Optionally, if the amount of carbohydrates, the amount of fat, the amount of sugar, or the amount of glycemic index varies from the recommended content of caloric consumption by a predefined amount, the second treatment session duration is greater than the treatment session duration.

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Optionally, if the appetite of the person varies from a target appetite level by a predefined amount, at least one of the second pulse width, the second pulse amplitude, the second pulse frequency, the second treatment session duration, and the second treatment session frequency is decreased relative to the pulse width, the pulse amplitude, the pulse frequency, the treatment session duration, and a second treatment session frequency.

Optionally, if the hunger of the person varies from a target hunger level by a predefined amount, at least one of the second pulse width, the second pulse amplitude, the second pulse frequency, the second treatment session duration, and the second treatment session frequency is decreased relative to the pulse width, the pulse amplitude, the pulse frequency, the treatment session duration, and a second treatment session frequency.

Optionally, if the satiety level of the person varies from a target satiety level by a predefined amount, at least one of the second pulse width, the second pulse amplitude, the second pulse frequency, the second treatment session duration, and the second treatment session frequency is decreased relative to the pulse width, the pulse amplitude, the pulse frequency, the treatment session duration, and a second treatment session frequency.

Optionally, if the satiation level of the person varies from a target satiation level by a predefined amount, at least one of the second pulse width, the second pulse amplitude, the second pulse frequency, the second treatment session duration, and the second treatment session frequency is decreased relative to the pulse width, the pulse amplitude, the pulse frequency, the treatment session duration, and a second treatment session frequency.

Optionally, if the fullness level of the person varies from a target fullness level by a predefined amount, at least one of the second pulse width, the second pulse amplitude, the second pulse frequency, the second treatment session duration, and the second treatment session frequency is decreased relative to the pulse width, the pulse amplitude, the pulse frequency, the treatment session duration, and a second treatment session frequency.

Optionally, the electrical dermal patch further comprises a transceiver and wherein said signal is caused to be transmitted to the electrical dermal patch wirelessly.

Optionally, said device is at least one of a mobile phone, a tablet computer, and a laptop computer.

In some embodiments, the present specification discloses a method of modulating at least one of a person’s appetite, hunger, satiety level, or satiation comprising: providing an electrical

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PCT/ÜS2016/019416 dermal patch adapted to adhere to the person’s epidermal layer, wherein said electrical dermal patch comprises a controller, at least one electrode adapted to be in electrical contact with said person’s epidermal layer, and a pulse generator in electrical communication with the controller and said at least one electrode; defining a first plurality of stimulation parameters; generating a plurality of electrical pulses using said first plurality of stimulation parameters, wherein said first plurality of stimulation parameters are defined such that, after applying at least one stimulation to the patient’s epidermal layer, at least one of the patient’s appetite, hunger, satiety level, and satiation level is modified; using an application installed on a device separate from die electrical dermal patch to acquire data, said data being indicative of at least one of the person’s appetite, hunger, satiety level, satiation level, fullness level, amount of caloric intake, weight, type of caloric intake, and timing of caloric intake; generating a signal, using said application, based upon said data; causing the signal to be transmitted to the electrical dermal patch; and generating a second plurality of electrical pulses using a second plurality of stimulation parameters, wherein said second plurality of stimulation parameters is determined.

Optionally, said first plurality of stimulation parameters and second plurality of stimulation parameters are further selected such that a post-stimulation daily caloric intake of said person decreases relative to a pre-stimulation daily caloric intake of said person, wherein said pre-stimulation daily caloric intake is a function of an amount of calories consumed by the person over a first predefined period of time prior to stimulation, and wherein said poststimulation daily caloric intake is a function of an amount of calories consumed by the person over a second predefined period of time equal in duration to the first predefined period of time, after stimulation is initiated.

Optionally, said first plurality of stimulation parameters and second plurality of stimulation parameters are further selected such that a post-stimulation daily caloric intake of said person is less than 99% of a pre-stimulation daily caloric intake of said person, wherein said pre-stimulation daily caloric intake is a function of an amount of calories consumed by the person over a first predefined period of time prior to stimulation, and wherein said poststimulation daily caloric intake is a function of an amount of calories consumed by the person over a second predefined period of time equal in duration to the first predefined period of time, after stimulation is initiated.

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PCT/ÜS2016/019416 level of the person decreases by at least 1% relative to a triglyceride level of the person before stimulation.

Optionally, said first plurality of stimulation parameters and second plurality of stimulation parameters are further selected such that, after at least one stimulation, a total blood cholesterol level of the person decreases by at least 1% relative to a total blood cholesterol level of the person before stimulation.

Optionally, said first plurality of stimulation parameters and second plurality of stimulation parameters are further selected such that, after at least one stimulation, a glycemia level of the person decreases by at least 1% relative to a glycemia level of the person before stimulation.

Optionally, said first plurality of stimulation parameters and second plurality of stimulation parameters are further selected such that, after at least one stimulation, a composition of the person’s gut microbiota modulates from a first state to a second state, wherein the first state has a first level of bacteroidetes and a first level of firmicutes, wherein the second state has a second level of bacteroidetes and a second level of firmicutes, wherein the second level of bacteroidetes is greater than the first level of bacteroidetes by at least 3%, and wherein the second level of firmicutes is less than the first level of firmicutes by at least 3%.

In some embodiments, the present specification discloses a method of enabling a person to comply with a diet plan comprising: providing an electrical dermal patch adapted to adhere to the person’s epidermal layer, wherein said electrical dermal patch comprises a controller, at least one electrode adapted to be in electrical contact with said patient’s epidermal layer, and a pulse generator in electrical communication with the controller and said at least one electrode; generating a plurality of electrical pulses having a treatment session duration and a treatment session frequency, wherein each of said plurality of electrical pulses is defined by pulse width, a pulse amplitude, a pulse shape, a pulse frequency and wherein said pulse shape, pulse width, said pulse amplitude, and said pulse frequency are selected to enable the person to comply with the diet plan; using an application installed on an external device to acquire data over a period of time, said data including at least one of a timing of caloric consumption, an amount of caloric consumption, a content of a caloric consumption, an appetite level, a timing of appetite, a hunger level, a satiety level, a satiation level, a fullness level, an amount of calories burned, and an activity level; after said period of time, generating a signal, using said application, based upon

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PCT/ÜS2016/019416 said data; causing the signal to be transmitted to the electrical dermal patch; generating a second plurality of electrical pulses using a plurality of stimulation parameters, said plurality of stimulation parameters being determined based upon said signal and including at least one of a second pulse width, a second pulse amplitude, a second pulse frequency, a second pulse duty cycle, a second pulse shape, a second treatment session duration, and a second treatment session frequency; using said application, causing at least a portion of at least one of said data and said plurality of stimulation parameters to be transmitted from said external device to a server; using said server to store said at least a portion of said data and said plurality of stimulation parameters in a database; using said server to associate at least a portion of said data and said plurality of stimulation parameters with an electronic profile of the patient; using said server to share said electronic profile of the patient with electronic profiles of other individuals; using said server to transmit to said application at least one of a timing of caloric consumption, an amount of caloric consumption, a content of a caloric consumption, an appetite level, a timing of appetite, a hunger level, a satiety level, a satiation level, a fullness level, an amount of calories burned, an activity level, and a plurality of stimulation parameters associated with one or more of said individuals; and visually displaying in said application at least one of a timing of caloric consumption, an amount of caloric consumption, a content of a caloric consumption, an appetite level, a timing of appetite, a hunger level, a satiety level, a satiation level, a fullness level, an amount of calories burned, an activity level, and a plurality of stimulation parameters associated with one or more of said individuals in association with or relative to at least one of the timing of caloric consumption, the amount of caloric consumption, the content of caloric consumption, the appetite level, the timing of appetite, the hunger level, the satiety level, the satiation level, the fullness level, the amount of calories burned, the activity level, and the plurality of stimulation parameters associated of the patient. It should be appreciated that server may refer to one or more computing devices, whether individually identifiable or collectively acting as a cloud service.

Optionally, in any of the above embodiments, the duty cycle may be between 1% and 100% and the pulse shape of any one of monophasic, biphasic, and sinusoidal. Additionally, in any of the above embodiments, each of the stimulation sessions may be further defined as having a stimulation session duration of 1 min to 120 min with 1 to 24 stimulation sessions per day and

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PCT/ÜS2016/019416 to 168 stimulation sessions per week. The stimulation session duration may also range from 1 min to substantially continuously.

Optionally, in any of the above embodiments, the stimulation sessions are configured to provide alternating stimulation sessions between a first session having a first pulse frequency equal to less than a pivot frequency, such as 50 Hz or a frequency in a range of 25 to 75 Hz, followed by a second session having a second pulse frequency greater than the pivot frequency.

Optionally, said control device is further configured to monitor, record, and modify stimulation parameters of said stimulation protocol. The control device may comprise any one of a smartphone, tablet, and personal digital assistant and may be in data communication with a remote patient care facility or patient care personnel.

Optionally, said control device includes a graphical user interface screen configured to receive appetite, eating, weight, and activity information data from a patient and display said data on said screen. Still optionally, said control device is configured to generate and display a plurality of charts and graphs representative of said information data and, based upon said data, manage and generate prompts related to patient compliance on said graphical user interface screen.

Optionally, said control device is adapted to receive and integrate exercise and weight loss information from a third party device.

Optionally, said control device is configured to provide rescue stimulation sessions, wherein a rescue stimulation session is defined as an on-demand stimulation session applied at the onset of unplanned hunger events or potential occurrences of hunger events as determined by analyzing said data.

Optionally, said stimulation device includes at least one sensor and said control device is configured to modify said stimulation parameters based on data received from said at least one sensor. The sensor may include any one or combination of a glucose sensor, a neural sensor, an accelerometer, an impedance sensor, and a bio-impedance sensor.

The present specification also discloses a device for providing electrical stimulation from the external surface of the patient’s epidermal layer through 5mm, 10mm, 15mm, 20mm, 25mm or any increment therein of the dermis comprising: a housing comprising a microprocessor, a wireless transceiver, a pulse generator, a power management module, and at least one electrode extending from within the housing or an external surface of the housing; at least one conductive

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PCT/ÜS2016/019416 pad configured to be in electrical communication with the electrode and be placed on a skin surface of a patient, wherein said at least one electrode is positioned such that an electrical field generated by said at least one electrode is shallow and widely distributed over said skin surface, wherein shallow is defined as a depth of no more than 25 mm from said skin surface and widely distributed is defined as at least an area of attachment of said at least one conductive pad to said skin surface, further wherein said device provides a maximum output voltage of 500 V and a maximum output current of 500 mA.

The pad may have a shape including any one of irregular, rectangular, circular, square, elliptical, and triangular and wherein, at its longest, a length of the pad ranges from 2 to 4 inches, at its widest, a width or diameter of said pad ranges from 1.25 to 3 inches, and a thickness of approximately 0.2 inches. In another embodiment, the electrode/pad combination may have a shape including any one of irregular, rectangular, circular, square, elliptical, and triangular and wherein, at its widest, would between 0.25 to 5 inches in width, at its tallest would be between 0.25 to 5 inches in height, and at its thickest would be between 0.25 to 5 inches in thickness. In another embodiment, the device would comprise two of such electrode/pad combinations placed side by side.

The present specification also discloses a device for treating a condition, including at least one of obesity, over-weight, eating disorders, metabolic syndrome and diabetes in a patient, wherein said device is configured to deliver electrical stimulation from the external surface of the patient’s epidermal layer through a range of 0.1 mm to 25 mm, or any increment therein, of the dermis by applying electrical stimulation to any one of an epidermis of a T2 frontal thoracic dermatome, an epidermis of a T3 frontal thoracic deimatome, an epidermis of a T4 frontal thoracic dermatome, an epidermis of a T5 frontal thoracic dermatome, an epidermis of a T6 frontal thoracic dermatome, an epidermis of a T7 frontal thoracic dermatome, an epidermis of a T8 frontal thoracic dermatome, an epidermis of a T9 frontal thoracic dermatome, an epidermis of a T10 frontal thoracic dermatome, an epidermis of a Til frontal thoracic dermatome, and an epidermis of a T12 frontal thoracic dermatome of said patient, further wherein electrical stimulation is increased based on data from a first parameter and electrical stimulation is decreased based on data from a second parameter. The first parameter may include any one of appetite, hunger, weight, body mass index (BM1), and body fat and said second parameter may include any one of nausea, dyspepsia, heartbum, and sensation at the site of stimulation.

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The present specification also discloses a device for treating a condition, including at least one of obesity, over-weight, eating disorders, metabolic syndrome and diabetes in a patient, wherein said device is configured to deliver electrical stimulation from the external surface of the patient’s epidermal layer through a range of 0.1 mm to 25 mm, or any increment therein, of the dermis by applying electrical stimulation to any one of an epidermis of a T2 frontal thoracic dermatome, an epidermis of a T3 frontal thoracic dermatome, an epidermis of a T4 frontal thoracic dermatome, an epidermis of a T5 frontal thoracic dermatome, an epidermis of a T6 frontal thoracic dermatome, an epidermis of a T7 frontal thoracic dermatome, an epidermis of a T8 frontal thoracic dermatome, an epidermis of a T9 frontal thoracic dermatome, an epidermis of a T10 frontal thoracic dermatome, an epidermis of a Til frontal thoracic dermatome, and an epidermis of a T12 frontal thoracic dermatome of said patient, further wherein electrical stimulation is decreased based on data indicative of excessive appetite loss, excessive hunger loss, an actual weight less than a target weight, an actual caloric intake less than a target caloric intake, an actual BMI less than a target BMI.

The present specification also discloses a device for treating a condition, including at least one of obesity, over-weight, eating disorders, metabolic syndrome and diabetes in a patient, wherein said device is configured to deliver electrical stimulation from the external surface of the patient’s epidermal layer through a range of 0.1 mm to 10 mm or a range of 0.1 mm to 20 mm of the dermis by applying electrical stimulation to any one of an epidermis of a T2 frontal thoracic dermatome, an epidermis of a T3 frontal thoracic dermatome, an epidermis of a T4 frontal thoracic dermatome, an epidermis of a T5 frontal thoracic dermatome, an epidermis of a T6 frontal thoracic dermatome, an epidermis of a T7 frontal thoracic dermatome, an epidermis of a T8 frontal thoracic dermatome, an epidermis of a T9 frontal thoracic dermatome, an epidermis of a T10 frontal thoracic dermatome, an epidermis of a Til frontal thoracic dermatome, and an epidermis of a T12 frontal thoracic dermatome of said patient, further wherein said patient is stimulated with a first stimulation algorithm to induce weight loss and a second stimulation algorithm to maintain weight loss, wherein a first total stimulation energy per day of said first stimulation algorithm is greater than a second total stimulation energy per day of said second stimulation algorithm.

The present specification also discloses a device for suppressing appetite or food cravings in a patient, said device comprising: a device body having a length no greater than 5 inches, a width no greater than 2 inches, and a height no greater than 1.5 inches, preferably no greater than 0.35 inches, and comprising a microprocessor, a wireless transceiver, a pulse generator, a power management module, and at least one electrode extending along a bottom surface of said device body; and wherein said device is configured to deliver electrical stimulation from the external surface of the patient’s epidermal layer through a range of 0.1 mm to 10 mm or a range of 0.1 mm to 20 mm of the dermis by applying electrical stimulation to any one of an epidermis of a T2 frontal thoracic dermatome, an epidermis of a T3 frontal thoracic dermatome, an epidermis of aT4 frontal thoracic dermatome, an epidermis of a T5 frontal thoracic dermatome, an epidermis of aT6 frontal thoracic dermatome, an epidermis of a T7 frontal thoracic dermatome, an epidermis of a T8 frontal thoracic dermatome, an epidermis of a T9 frontal thoracic dermatome, an epidermis of a T10 frontal thoracic dermatome, an epidermis of a Tl 1 frontal thoracic dermatome, and an epidermis of a T12 frontal thoracic dermatome of said patient; and wherein said device is programmed with a stimulation protocol for providing electrical stimulation to said patient, wherein said stimulation protocol is configured to provide stimulation non-continuously and for at least two stimulation sessions per week, wherein each of said stimulation sessions has an on period of 10 to 120 minutes or substantially continuously.

The present specification also discloses an electrical dermal patch configured to modulate at least one of an appetite, hunger, satiety level, or satiation level of a patient. The electrical dermal patch comprises a housing adapted to be adhered to the patient’s epidermal layer and configured to be placed on the patient’s front thoracic dermatomes; a controller positioned within tire housing; at least one electrode adapted to be in electrical contact with said patient’s epidermal layer; and, a pulse generator positioned within the housing and in electrical communication with the controller and said at least one electrode, wherein the pulse generator is configured to generate a plurality of electrical pulses, said plurality of electrical pulses being defined by a plurality of stimulation parameters, wherein said plurality of stimulation parameters are selected such that at least one of the patient’s appetite, hunger, satiety level, and satiation level modulates from a first state, prior to stimulation, to a second state after stimulation.

The present specification also discloses an electrical stimulation system configured to modulate at least one of a patient’s appetite, hunger, level of satiety, or level of satiation level. The electrical stimulation system comprising an electrical dermal patch adapted to be adhered to the patient’s epidermal layer and configured to be placed on the patient’s front thoracic dermatomes,

Date Reçue/Date Received 2022-06-08 wherein said electrical dermal patch comprises a controller, at least one electrode adapted to be in electrical contact with an epidermal layer of said patient, a pulse generator in electrical communication with the controller and said at least one electrode; and a transceiver in communication with at least one of said controller and pulse generator; and a plurality of programmatic instructions, stored in a non-transient computer readable memory of a device physically separate from said electrical dermal patch, wherein, when executed, said programmatic instructions acquire patient status data, generate a modulation signal based upon said patient status data, wherein said modulation signal comprises instructions for modulating at least one of a pulse width, a pulse amplitude, a pulse frequency, a pulse shape, a duty cycle, a session duration, and a session frequency, and wirelessly transmit said modulation signal from the device to the transceiver.

The present application also discloses An electrical dermal patch configured to modulate at least one of an appetite, hunger, satiety level, or satiation level of a patient, comprising a housing adapted to be adhered to the patient’s epidermal layer and configured to be placed on the patient’s front thoracic dermatomes; a controller positioned within the housing; at least one electrode adapted to be in electrical contact with said patient’s epidermal layer; a pulse generator positioned within the housing and in electrical communication with the controller and said at least one electrode, wherein the pulse generator is configured to generate a plurality of electrical pulses, said plurality of electrical pulses being defined by a plurality of stimulation parameters, wherein said plurality of stimulation parameters are selected such that at least one of die patient’s appetite, hunger, satiety level, and satiation level modulates from a first state, prior to stimulation, to a second state after stimulation; and a transceiver in electrical communication with the controller, wherein the transceiver is configured to communicate wirelessly with an external device and to receive a signal from the external device, wherein the signal is representative of at least one parameter of the plurality of electrical pulses and wherein said at least one parameter is at least one of a pulse width, a pulse amplitude, a pulse frequency, a pulse shape, a stimulation session duration, a duty cycle, or a stimulation session frequency.

The aforementioned and other embodiments of the present specification shall be described in greater depth in the drawings and detailed description provided below.

BRIEF DESCRIPTION OF THE DRAWINGS

77a

Date reçue/Date received 2023-05-26

These and other features and advantages of the present specification will be further appreciated, as they become better understood by reference to die following detailed description when considered in connection with the accompanying drawings:

FIG. 1A is a block diagram of a system for stimulating nerves and nerve endings in body 5 tissue, in accordance with various embodiments of the present specification;

FIG. IB is a block diagram of a system for stimulating or modulating nerves and nerve endings in body tissues, in accordance with another embodiment of the present specification;

FIG. IC is a block diagram of a system for stimulating or modulating nerves and nerve endings in body tissues, in accordance with yet another embodiment of the present specification;

FIG. ID is a block diagram of a system for stimulating or modulating nerves and nerve endings in body tissues, in accordance with yet another embodiment of Ihe present specification;

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FIG. IE is a block diagram of a system for stimulating or modulating nerves and nerve endings in body tissues, in accordance with still another embodiment of the present specification;

FIG. IF is a block diagram of a system for stimulating or modulating nerves and nerve endings in body tissues, in accordance with yet another embodiment of the present specification;

FIG. 2A is a side perspective view of an electro-dermal patch (EDP) device, in accordance with some embodiments of the present specification;

FIG. 2B is a front perspective view of the electro-dermal patch device of FIG. 2 A;

FIG. 2C is a top perspective view of the electro-dermal patch device of FIG. 2A;

FIG. 2D is an oblique perspective view of an electro-dermal patch with hydrogel removed and a replacement hydrogel with liners, in accordance with one embodiment of the present specification;

FIG. 3 A illustrates a first pattern of electrodes, in accordance with certain embodiments;

FIG. 3B illustrates a second pattern of electrodes, in accordance with certain embodiments;

FIG. 4A is a perspective view of an electro-dermal patch device configured to provide electrical stimulation therapy, in accordance with some embodiments;

FIG. 4B is a side perspective view of an electro-dermal patch device, in accordance with another embodiment of the present specification;

FIG. 4C is a bottom perspective view of the electro-dermal patch device of FIG. 4B;

FIG. 4D is an oblique, top perspective view of an electro-dermal patch device, in accordance with another embodiment of the present specification;

FIG. 4E is an oblique, top perspective view of the controller assembly of the electrodermal patch device of FIG. 4D;

FIG. 4F is an oblique, bottom perspective view of the controller assembly of the electrodermal patch device of FIG. 4D;

FIG. 4G is a side perspective cross-sectional view of an electro-dermal patch device comprising a capacitance type connection (dielectric material) between the electrode contacts and a hydrogel of the electrode assembly, in accordance with one embodiment of the present specification;

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FIG. 4H is an oblique, top perspective view of the controller assembly of the electrodermal patch device of FIG. 4D with a portion of the overmold cut away to expose additional components of the controller assembly;

FIG. 41 is an oblique, top perspective view of the electrode assembly of the electrodermal patch device of FIG. 4D;

FIG. 4J is an oblique, bottom perspective view of the electro-dermal patch device of FIG. 4D;

FIG. 4K is a side perspective view of the electro-dermal patch device of FIG. 4D;

FIG. 4L is an oblique, top perspective, short axis cross-sectional view of the electrodermal patch device of FIG. 4D;

FIG. 4M is a front perspective cross-sectional view of the electro-dermal patch device of FIG. 4D;

FIG. 4N is an oblique, top perspective, long axis cross-sectional view of the electrodermal patch device of FIG. 4D;

FIG. 40 is a side perspective cross-sectional view of the electro-dermal patch device of FIG. 4D,

FIG. 4P illustrates a first pattern of electrodes of tire electro-dermal patch device of FIG. 4D, in accordance with an embodiment;

FIG. 4Q illustrates a second pattern of electrodes of the electro-dermal patch device of FIG. 4D, in accordance with an embodiment;

FIG. 4R illustrates a third pattern of electrodes of the electro-dermal patch device of FIG. 4D, in accordance with an embodiment;

FIG. 4S illustrates a fourth pattern of electrodes of the electro-dermal patch device of FIG. 4D, in accordance with an embodiment;

FIG. 5A is an oblique, top perspective view of an electro-dermal patch device in accordance with some embodiments;

FIG. 5B is a side perspective view of the EDP device of FIG. 5 A;

FIG. 5C is a bottom view of the EDP device of FIG. 5 A;

FIG. 5D is an oblique, top perspective view of the EDP device of FIG. 5 A with a portion of an overmold removed;

FIG. 5E is a side cross-sectional view of the EDP device of FIG. 5D;

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FIG. 5F is a top perspective view of the EDP device of FIG. 5 A with the entire overmold removed;

FIG. 6A illustrates an electro-dermal patch device of the present specification, configured as a skin patch, placed at a lateral thoracic dermatome and being wirelessly controlled by a smartphone, in accordance with various embodiments;

FIG. 6B is a schematic diagram of a plurality of electro-dermal patch users with companion devices shared over a common network connection, in accordance with one embodiment of the present specification;

FIG. 6C is a flow chart listing the steps in one embodiment of a method of aggregating, organizing, and analyzing stimulation parameters and patient hunger, appetite, and well-being scores for a plurality of patients, each having an EDP device with linked companion device connected to an aggregate patient network;

FIG. 6D is a flow chart illustrating the steps involved in using one or more downloadable applications to configure and reconfigure stimulation provided by an electro-dermal patch (EDP) device, in accordance with one embodiment of the present specification;

FIG. 7 is a screen shot of a companion device depicting a diary widget, in accordance with one embodiment of the present specification;

FIG. 8 is a screen shot of a companion device depicting a list view of diary entries, in accordance with one embodiment of the present specification;

FIG. 9 is a screen shot of a companion device depicting a calendar view of diary entries, in accordance with one embodiment of the present specification;

FIG. 10 is a screen shot of a companion device depicting a quick entry buttons view, in accordance with one embodiment of the present specification;

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FIG. 11 is a screen shot of a companion device depicting an appetite entry screen, in accordance with one embodiment of the present specification;

FIG. 12 is a screen shot of a companion device depicting an exercise entry screen, in accordance with one embodiment of the present specification;

FIG. 13 is a screen shot of a companion device depicting a hunger entry screen, in accordance with one embodiment of the present specification;

FIG. 14 is a screen shot of a companion device depicting a stimulation session entry screen, in accordance with one embodiment of the present specification;

FIG. 15 is a screen shot of a companion device depicting a weight entry screen, in accordance with one embodiment of the present specification;

FIG. 16 is a screen shot of a companion device depicting a well-being entry screen, in accordance with one embodiment of the present specification;

FIG. 17A is an illustration depicting the distribution of the front and lateral T2 - T12 dermatomes across a thorax and abdomen of a human body;

FIG. 17B is an illustration depicting the distribution of the anterior and posterior C5 - T1 dermatomes across a hand, arm and upper chest regions of a human body;

FIG. 17C is an illustration depicting the distribution of the C5 - T1 dermatomes across the ventral side of the hand and lower arm of the human body;

FIG. 18A illustrates T6 stimulation using an electro-dermal patch device, in accordance with certain embodiments;

FIG. 18B illustrates T7 stimulation using an electro-dermal patch device, in accordance with certain embodiments;

FIG. 18C illustrates T6 and T7 stimulation using an electro-dermal patch device, in accordance with certain embodiments;

FIG. 19A illustrates C8 stimulation position of the ventral or front (palm) side of a user’s hand using an electro-dermal patch, in accordance with certain embodiments;

FIG. 19B illustrates C8 stimulation position of the dorsal or back side of the user’s hand using an electro-dermal patch, in accordance with certain embodiments;

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FIG. 19C illustrates C8 and T1 stimulation position of the ventral side of the user’s lower arm or wrist regions using an electro-dermal patch, in accordance with cartain embodiments;

FIG. 20A illustrates an embodiment of an electro-dermal patch device of die present specification wrapped around the edge of the user’s hand for stimulating the C8 dermatome;

FIG. 20B illustrates another embodiment of an electro-dermal patch device of the present specification wrapped around the edge of the user’s hand for stimulating the C8 dermatome;

FIG. 21A is a perspective view of a band incorporating an EDP (electro-dermal patch) device of the present specification, in accordance with an embodiment;

FIG. 21B is a perspective view of a wristwatch incorporating an EDP device of the present specification, in accordance with an embodiment;

FIG. 22A illustrates a first embodiment of a hand glove incorporating one or more EDP devices of the present specification;

FIG. 22B illustrates a second embodiment of a pair of hand gloves incorporating one or more EDP devices of the present specification;

FIG. 22C illustrates a third embodiment of a pair of hand gloves incorporating one or more EDP devices of the present specification;

FIG. 22D illustrates a fourth embodiment of a hand glove incorporating at least one EDP device of the present specification;

FIG. 23 is a perspective view of hand gear incorporating at least one EDP device of the present specification, in accordance with an embodiment;

FIG. 24 is a perspective view of a finger ring incorporating an EDP device of the present specification, in accordance with an embodiment;

FIG. 25 illustrates a squeezable ball incorporating an EDP device of the present specification, in accordance with an embodiment;

FIG. 26 illustrates hand gear incorporating an EDP device of the present specification, in accordance with an embodiment;

FIG. 27A is a flow chart illustrating the steps involved in a method of determining stimulation reaction thresholds and using an electro-dermal patch (EDP) device to suppress appetite in a patient, in various embodiments of the present specification;

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FIG. 27B is a flow chart illustrating the steps involved in a method of determining stimulation reaction thresholds and using an electro-dermal patch (EDP) device to suppress appetite in a patient, in various embodiments of the present specification;

FIG. 27C is a flow chart illustrating the steps involved in a method of using an electrodermal patch device to suppress appetite in a patient, in various embodiments of the present specification;

FIG. 28 is a flow chart illustrating the steps involved in a method of using an electrodermal patch device to suppress appetite in a patient, in various embodiments of the present specification;

FIG. 29 is a flow chart illustrating the steps involved in a method of using an electrodermal patch device to suppress appetite in a patient, in various embodiments of the present specification;

FIG. 30 is a flow chart illustrating the steps involved in a method of using an electrodermal patch device to suppress appetite in a patient, in various embodiments of the present specification;

FIG. 31 is a flow chart illustrating the steps involved in a method of using an electrodermal patch device to suppress appetite in a patient, in various embodiments of the present specification;

FIG. 32 is a flow chart illustrating the steps involved in methods of using an electrodermal patch device to suppress appetite in a patient, in various embodiments of the present specification;

FIG. 34 is a flow chart illustrating steps involved in methods of using an electro-dermal patch device to suppress appetite in a patient, in various embodiments of the present specification;

FIG. 35A is a Visual Analogue Scale (VAS) questionnaire for assessing a feeling of hunger or appetite, in accordance with an embodiment;

FIG. 35B is a VAS questionnaire for assessing a feeling of fullness, in accordance with an embodiment;

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FIG. 35C is a VAS questionnaire for assessing a feeling of satiation, in accordance with an embodiment;

FIG. 35D is a VAS questionnaire for assessing a feeling of satiety, in accordance with an embodiment;

FIG. 36A is a graph illustrating pre-stimulation and post-stimulation hunger profiles of a first patient, in accordance with an embodiment;

FIG. 36B is a graph illustrating pre-stimulation and post-stimulation hunger profiles of a second patient, in accordance with an embodiment;

FIG. 36C is a graph illustrating pre-stimulation and post-stimulation hunger profiles of a third patient, in accordance with an embodiment;

FIG. 36D is a graph illustrating pre-stimulation and post-stimulation hunger profiles of a fourth patient, in accordance with an embodiment;

FIG. 36E is a graph illustrating pre-stimulation and post-stimulation hunger profiles of a fifth patient, in accordance with an embodiment;

FIG. 36F is a graph illustrating median AUC (Area Under the Curve) hunger scores for pre-stimulation, end-of-stimulation and post-stimulation scenarios;

FIG. 36G is a graph illustrating pre-stimulation and post-stimulation hunger profiles over an extended period of time, in accordance with a first embodiment;

FIG. 36H is a graph illustrating pre-stimulation and post-stimulation hunger profiles over an extended period of time, in accordance with a second embodiment;

FIG. 361 is a graph illustrating hunger scores for pre-stimulation, end-of-stimulation and post-stimulation scenarios;

FIG. 37A is a graph illustrating pre-stimulation and post-stimulation satiety profiles of a first patient, in accordance with an embodiment;

FIG. 37B is a graph illustrating pre-stimulation and post-stimulation satiety profiles of a second patient, in accordance with an embodiment;

FIG. 37C is a graph illustrating pre-stimulation and post-stimulation satiety profiles of a third patient, in accordance with an embodiment;

FIG. 37D is a graph illustrating pre-stimulation and post-stimulation satiety profiles of a fourth patient, in accordance with an embodiment;

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FIG. 37E is a graph illustrating pre-stimulation and post-stimulation satiety profiles of a fifth patient, in accordance with an embodiment;

FIG. 37F is a graph illustrating median AUC (Area Under the Curve) satiety scores for pre-stimulation, end-of-stimulation and post-stimulation scenarios;

FIG. 37G is a graph illustrating pre-stimulation and post-stimulation satiety profiles over an extended period of time, in accordance with a first embodiment;

FIG. 37H is a graph illustrating pre-stimulation and post-stimulation satiety profiles over an extended period of lime, in accordance with a second embodiment;

FIG. 371 is a graph illustrating satiety scores for pre-stimulation, end-of-stimulation and post-stimulation scenarios;

FIG. 38A is a graph illustrating exercise scores of a sample of patients treated with stimulation therapy, in accordance with an embodiment of the present specification;

FIG. 38B is a graph illustrating weights of a sample of patients treated with stimulation therapy, in accordance with an embodiment of the present specification;

FIG. 38C is a graph illustrating BMIs (Body Mass Index) of a sample of patients treated with stimulation therapy, in accordance with an embodiment of the present specification;

FIG. 38D is a graph illustrating appetite scores of a sample of patients treated with stimulation therapy, in accordance with an embodiment of the present specification;

FIG. 38E is a graph illustrating dietaiy compliance scores of a sample of patients treated with stimulation therapy, in accordance with an embodiment of the present specification;

FIG. 38F is a graph illustrating well-being scores of a sample of patients treated with stimulation therapy, in accordance with an embodiment of the present specification;

FIG. 39 is a side view illustration of an EDP device, in accordance with a less preferred embodiment;

FIG. 40 is a side view illustration of another EDP device, in accordance with a less preferred embodiment;

FIG. 41 is a side view illustration of still another EDP device, in accordance with a less preferred embodiment;

FIG. 42 is a side view illustration of yet another EDP device, in accordance with a less preferred embodiment;

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FIG. 43 is an illustration of a percutaneous multi-electrode array that may be employed with the devices of the present specification;

FIG. 44 is a block diagram of a mobile electronics platform that may be employed with the devices of the present specification;

FIG. 45 is an illustration of an EDP device that receives wireless energy for stimulation, in accordance with a less preferred embodiment;

FIG. 46 is an illustration of another EDP device that receives wireless energy for stimulation, in accordance with a less preferred embodiment;

FIG. 47A is a bar graph illustrating mean cumulative changes of antral motility indices for various stimulation sessions, in accordance with an embodiment; and,

FIG. 47B is a bar graph illustrating maximum plasma endorphin levels measured for various stimulation sessions, in accordance with an embodiment.

DETAILED DESCRIPTION

The present specification is directed toward systems and methods of modulating a patient’s appetite, hunger, satiety level, satiation level, or fullness level by delivering electrical stimulation to a predetermined area of the user’s anatomy in a manner that is convenient, easy to use, and amenable to increased patient compliance. The term “modulating” refers to any form of regulation, manipulation or control to change a given variable from one state to another state. More particularly, the present specification relates to electrical stimulation devices comprising low profile, wearable, disposable skin patches that are configured for placement on a patient’s front and lateral T2 to T12 and/or C5-T1 dermatomes, easy to self-administer, programmable and monitorable using a mobile handheld device, and programmed to stimulate, from the external surface of the patient’s epidermal layer through a range of 0.1 mm to 10 mm of the dermis or through a range of 0.1 mm to 20 mm of the dermis, nerves located proximate to the front and lateral T2 to T12 and/or C5-T1 dermatomes in a manner that enables modulation of a patient’s appetite, hunger, satiety level, satiation level or fullness level, and that avoids nausea, dyspepsia and minimizes habituation. In various embodiments, a stimulation depth through the patient’s epidermal layer ranges from 0.1 mm to 0.5,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17,18, 19, 20 mm or any increment therein. The present specification further relates to a low profile, wearable, disposable skin patch that is capable of integrating with, and being controlled

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PCT/ÜS2016/019416 by, a plurality of different hardware devices or software applications depending on the type, extent, nature and scope of the appetite, hunger, satiety level, satiation level or fullness level modulation desired, including immediate, large weight loss or long term weight maintenance.

An electrical neuro-stimulation device, in the form of an electro-dermal patch (EDP) is disclosed that, in various embodiments, is configured as a discrete, disposable and waterproof adhesive patch or pad for placement on a user’s skin, particularly on the regions encompassing the front and lateral T2 - T12 dermatomes and/or C5-T1 dermatomes. In various embodiments, the EDP is wireless and incorporates flexible circuits and elastomeric overmolding, making the device waterproof and flexible enough to be able to mold to body contours for greater comfort and permanent wearability. In some embodiments, the EDP device also modulates ghrelin production.

In accordance with various aspects of the present specification, the resultant benefits of modulating appetite, hunger, satiety level, satiation level or fullness level include treating conditions associated with persons who are overweight or those with metabolic syndrome, treating obesity and T2DM prevention or management. In accordance wilh various aspects of the present specification, the electro-dermal patch device treats people having a BMI (Body Mass Index) of 25 or greater (overweight being 25-30, obese being 30 and above, and morbid obesity being above 35). In embodiments of the present specification, the electro-dermal patch device is wearable and can be controlled and programmed by the patient, allowing the patient to administer therapy and eliminating the need for frequent patient visits to a medical professional. In embodiments, the electro-dermal patch device is designed to be placed on the front and lateral thoracic dermatomes and/or C5 - T1 dermatomes of the patient. Therefore, the patient is able to place the electro-dermal patch device on him or herself, without the assistance of a medical professional.

In embodiments, the electro-dermal patch device is wirelessly coupled to a companion device (e.g. smartphone, watch, glove, wristband or tablet) which can be used to program the electro-dermal patch device, allowing the patient to self-administer therapy on-demand. In some embodiments, all therapy provided by the electro-dermal patch device is coupled with a storage or recording (for keeping a log of the therapy) and patient compliance reminders. The benefits provided by having a wearable and self-administered electro-dermal patch device include, among others, greater patient independence and improved patient compliance to stimulation protocols,

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PCT/ÜS2016/019416 with resultant increased dietary compliance and overall efficacy, and the ability to modify stimulation parameters based on real-time feedback provided to the electro-dermal patch device by the patient and other devices. In some embodiments, the electro-dermal patch device is driven by an algorithm derived from patient input data and monitored data (e.g. exercise monitored by a separate device). Adjustments to the algorithm, and therefore stimulation, are made both manually by the patient and automatically by the device itself or the companion device. In some embodiments, the electro-dermal patch device is driven by an algorithm derived from patient input data and monitored data (e.g. exercise monitored by a separate device). In some embodiments, the algorithm is also derived from monitored parameters, such as leptin (for ghrelin suppression), glucagon-like peptide 1 (GLP-1), hemoglobin A1C, and blood glucose levels (for diabetes treatment), lipids, and triglycerides. These parameters are measured at baseline and over time during treatment and are used as inputs to titrate therapy. Adjustments to the algorithm, and therefore stimulation, are made either manually by the patient or automatically by the electro-dermal patch device itself or the companion device or both. In accordance with some aspects of the present specification, a medical professional can flexibly program the electro-dermal patch and still direct the patient, only allowing the patient to adjust device parameters (for greater patient independence) but within restricted bounds or predetermined parameters.

The present specification is directed towards multiple embodiments. The following disclosure is provided in order to enable a person having ordinary skill in the art to practice the invention. Language used in this specification should not be interpreted as a general disavowal of any one specific embodiment or used to limit the claims beyond the meaning of the terms used therein. The general principles defined herein may be applied to other embodiments and applications without departing from the spirit and scope of the invention. Also, the terminology and phraseology used is for the purpose of describing exemplary embodiments and should not be considered limiting. Thus, the present invention is to be accorded the widest scope encompassing numerous alternatives, modifications and equivalents consistent with the principles and features disclosed. For purpose of clarity, details relating to technical material that is known in the technical fields related to the invention have not been described in detail so as not to unnecessarily obscure the present invention.

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For purposes of the present specification, the terms “trigger” and “triggering” do not necessarily imply immediately triggering stimulation. “Trigger” and “triggering” are defined as initiating or starting the execution of a protocol that will result in stimulation over a predefined period.

In the description and claims of the application, each of the words comprise11 include and have, and forms thereof, are not necessarily limited to members in a list with which the words may be associated.

As used herein, the indefinite articles a and an mean at least one or one or more unless the context clearly dictates otherwise.

The terms “patient”, “individual”, “person”, and “useri’ are used interchangeably throughout this specification and refer to the person that is receiving treatment or stimulation from the devices and methods of the present specification.

The term “hunger“ is defined as a physical sensation indicative of a person’s physical need for food and may be related to low levels of glucose in the person’s blood and/or concentrations of ghrdin and/or hunger-inducing gut hormones.

The term “appetite” is defined as a desire for food, possibly prompted by an emotional, psychological, and/or sensory reaction to the look, taste, or smell of food.

The term “satiation” is defined as a sensation of fullness that results in cessation of eating.

The term “fullness” is defined as a sensation of an adequate amount of food present in the stomach, ft should be appreciated that the term “fullness” refers to a psychological or perceptive sensation by the patient, which may be objectively measured using the scales described herein. The term “physiological fullness” shall refer to a physical measurement of the actual contents of a person’s stomach.

The term “satiety” is defined as a sense of fullness that prolongs the time between meals (the more satiety, the longer duration between two meals), ft is intended to refer to a patient’s perception of a sense of fullness that prolongs the time between meals.

The phrase “change in satiety” is defined as an alteration in the patient’s perception of gastric fullness or emptiness.

The term “dietary compliance” is defined as a patient’s ability to adhere to a prescribed regimen of caloric intake, whether defined in terms of total permissible calories or a type or

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PCT/ÜS2016/019416 amount of nutritional intake, or some combination thereof, in order to achieve a targeted daily, weekly, or monthly calorie consumption and/or a targeted type or amount of nutritional intake.

The phrase “weight maintenance” means adjusting an appetite or hunger suppression/decrease goal in order to maintain a certain amount of weight loss that has already been achieved and to now avoid gaining weight. In some embodiments, weight loss maintenance entails engaging in a surgical procedure (such as various bariatric surgeries), applying the EDP of the present specification and using appetite or hunger suppression/decrease in order to maintain the weight loss achieved by surgery.

The term “microbiota” is defined as an ensemble of microorganisms that reside in a previously established environment, such as the stomach or gastrointestinal system. The term “gut microbiota” or “gut flora is the name given to die microbiota living in a person’s intestine.

The term “glycemic index (GI)” is defined as a number associated with a particular type of food that indicates the food's effect on a person's blood glucose (also called blood sugar) level. A value of 100 represents the standard, an equivalent amount of pure glucose. The glycemic index is calculated by determining the incremental area under the blood glucose response curve of a specific portion of a test food expressed as a percent of the response to the same amount of carbohydrate from a standard food taken by the same subject.

The term “glycemic load (GL)” is defined as the glycemic index multiplied by grams of carbohydrate per serving size. GL is based on a specific quantity and carbohydrate content of a test food and calculated by multiplying the weighted mean of the dietary glycemic index by the percentage of total energy from the test food. When the test food contains quantifiable carbohydrates, the GL = GI (%) x grams of carbohydrate per serving.

The term “epidermal layer” means the outer most layer of a person’s skin and shall be construed to cover all variants of the word “epidermal”, including epidermis.

Throughout this specification, the term “power source” is used to represent any energy providing device, including a lithium-ion battery, a betavoltaic battery, a solar ceil, nickelcadmium battery, a fuel cell, a mobile phone, or remote charging station.

The term “controller” is used to denote a processing unit configured to control the initiation of stimulation, termination of stimulation, and type and/or extent of stimulation and shall include the terms “control unit”, “processing unit”, “microcontroller”, “microprocessor”, or “processor”.

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The term “pulse generator” means a device configured to generate electrical pulses in accordance with instructions from a controller. It should be appreciated that the pulse generator and controller can be integrated into a single device or multiple devices.

The term “electrode” is used to refer to a conducting material that is capable of receiving electrical pulses and communicating them to another surface.

The term “modulation” or “modulating” means any form of regulation, manipulation or control to change a given variable from one state to another state.

Any increases or decreases in levels or rates are determined by the following formula [(New Level or Rate) - (Old Level or Rate)]/(Old Level or Rate).

The phrase “at least one of x, y, and z” means that only one of x or y or z need to be true or present in order to satisfy that limitation.

The term “dermatome” refers to an area of skin that is primarily innervated and/or supplied by a specific spinal nerve.

The term “meridian” refers to low resistance fluid channels where various chemical and physical transports take place and are individual pathways which exist among the subcutaneous tissues and serve as channels for the flow of interstitial microscopic fluid throughout the body.

PCT/ÜS2016/019416

Table 1

<td> Parameter</td><td> Sensor</td>

<td> Heart Rate/Pulse Rate</td><td> EKG (2 Electrodes)/BVP (LED Emitter and Optical Sensor)</td>

<td> Beat-to-Beat Variability</td><td> EKG (2 Electrodes)</td>

<td> EKG Skin Surface Potential</td><td> EKG (3-10 Electrodes)</td>

<td> Respiration Rate</td><td> Chest Volume Change (Strain Gauge)</td>

<td> Skin Temperature</td><td> Surface Temperature Probe (Thermistors)</td>

<td> Core Temperature</td><td> Esophageal or Rectal Probe (Thermistors)</td>

<td> Heat Flow</td><td> Heat Flux (Thermopile)</td>

<td> Galvanic Skin Response</td><td> Skin Conductance (2 Electrodes)</td>

<td> EMG Skin Surface Potential</td><td> EMG (3 Electrodes)</td>

<td> EEG Skin Surface Potential</td><td> EEG (Multiple Electrodes)</td>

<td> EOG Eye Movement</td><td> Thin Film Piezoelectric Sensors</td>

<td> Blood Pressure</td><td> Electronic Sphygmomanometer</td>

<td> Body Fat</td><td> Body Impedance (2 Active Electrodes)</td>

<td> Activity</td><td> Accelerometer</td>

<td> Oxygen Consumption</td><td> Oxygen Uptake (Electro-chemical)</td>

<td> Glucose Level</td><td> Electro-chemical sensors, Optical techniques, Aqueous techniques (tears, saliva, and sweat), and Iontophoresis techniques.</td>

<td> Body Position</td><td> Mercury Switch Array, Accelerometer</td>

<td> Muscle Pressure</td><td> Thin Film Piezoelectric Sensors</td>

<td> UV Radiation</td><td> UV Sensitive Photo Cells</td>

<td> Blood oxygen saturation</td><td> Pulse oximeter</td>

The microprocessor 112 is programmed to summarize and analyze the data representative of the physiological parameters of the individual. For example, the microprocessor 112 can be 5 programmed to calculate an average, minimum or maximum heart rate or respiration rate over a defined period of time, such as ten minutes. The electro-dermal patch device 110 is also able to derive information relating to the individual's physiological state based on the data representative of one or more physiological parameters. The microprocessor 112 is programmed to derive such 94

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PCT/ÜS2016/019416 information using known methods based on the data representative of one or more physiological parameters. Table 2 provides examples of the type of information that can be derived, and indicates some of the types of data that can be used therefor.

Table 2

<td> Derived Information</td><td> Data Used</td>

<td> Activity level</td><td> Heart rate, pulse rate, respiration rate, heat flow, activity, oxygen consumption</td>

<td> Basal metabolic rate</td><td> Heart rate, pulse rate, respiration rate, heat flow, activity, oxygen consumption, glucose level</td>

<td> Basal temperature</td><td> Skin temperature, core temperature</td>

<td> Calories burned</td><td> Heart rate, pulse rate, respiration rate, heat flow, activity, oxygen consumption</td>

<td> Maximum oxygen consumption rate</td><td> EKG, heart rate, pulse rate, respiration rate, heat flow, blood pressure, activity, oxygen consumption</td>

<td> Relaxation Level</td><td> EKG, beat-to-beat variability, heart rate, pulse rate, respiration rate, skin temperature, heat flow, galvanic skin response, EMG, EEG, blood pressure, activity, oxygen consumption</td>

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PCT/ÜS2016/019416 physical inputs or sensors on the EDP 140 itself. The remaining inputs are on the companion device 105 and are actuated through the wireless coupling of the companion device 105 and EDP 140.

In some embodiments, rather than including a physical on/off switch, the EDP 140 depicted in FIG. IB is always using at least a minimum amount of power such that an ‘off* state refers to a low power state. While no stimulation is being provided, there is, at a minimum, a periodic ‘wake-up’ of the EDP 140 to check for communication from the companion device 105. The ‘wake-up’ places the device in an ‘on’ state and, in some embodiments, includes no stimulation wherein the EDP 140 runs diagnostics for reporting to the companion device 105. Therefore, while in the ‘ofF state, the EDP 140 is constantly using a very low amount of power, is not providing stimulation, and is either awaiting a signal from the companion device or is performing diagnostics or other non-stimulation activities requiring very little power. In some embodiments, the energy usage is less than 5 μΑ average current or in the range of 0.1 μΑ to 5 μΑ average current while in the ‘ofF state and greater than 10 μΑ average current while in the ‘on’ state. In some embodiments, the energy usage is at least 1 μΑ greater while in the ‘on’ state than while in the ‘ofF state. Once the EDP 140 receives a signal from the companion device 105 to initiate stimulation, it enters the ‘on’ state and uses an amount of energy associated with the level of stimulation. In another embodiment, the EDP 140 uses no energy while in an ‘ofF state and must be awakened, or switched to an ‘on’ state, by a signal from the companion device.

FIG. IC is a block diagram illustration of a system 161 for stimulating or modulating nerves and nerve endings in body tissues, in accordance with yet another embodiment of the present specification, hi some embodiments, referring to FIG. IC, the electro-dermal patch device (EDP) 160 includes a microcontroller 162, wireless transceiver 164, a power management module 170, such as a lithium-ion battery, a betavoltaic battery, a solar cell, nickel-cadmium battery, or a fuel cell, a pulse generator 166, one electrode 168, an optional single actuator 172 to turn the EDP 160 on or off, one sensor 175 for sensing a physiological parameter of the patient, and includes no other physical inputs on the EDP 160 itself. In one embodiment, the sensor 175 is a neural sensor. The remaining inputs are on the companion device 105 and are actuated through the wireless coupling of the companion device 105 and EDP 160.

In accordance with various aspects of the present specification, each component (power management module, microprocessor or microcontroller, pulse generator, transceiver, and one or

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PCT/ÜS2016/019416 more electrodes) of the electro-dermal patch may be positioned in a separate housing, in a separate device, or otherwise physically remote from each other. For example, as described with reference to FIG. 1A, the electro-dermal patch device 110 comprises a power management module 120, microprocessor or microcontroller 112, pulse generator 116, transceiver 114, and one or more electrodes 118 in a housing 111, where the one or more electrodes 118 are in physical communication with a hydrogel pad.

However, in a first alternative embodiment as shown in FIG. ID, the electro-dermal patch device 180 comprises a transceiver 182 having an antenna 184 for receiving electrical pulse signals 186 and an electrode 183, which may or may not be in physical contact with a hydrogel pad. A housing 181 may be positioned around the transceiver 182 and electrode 183 or a substrate carrier may be used to support a low-profile transceiver and/or electrode circuit without any additional housing structure. In this embodiment, an external device 185 comprises the power source, controller, and pulse generator adapted to generate a plurality of electrical pulses, as described earlier with reference to FIGS. 1A through IC. The external device 185 may be a watch, mobile phone, a sensor pod configured to attach to the patient using a strap or band, or other wearable device. The external device 185 wirelessly transmits the electrical pulses 186 to the transceiver 182 which, in turn, transmits the electrical pulses to the electrode 183 and, thereafter, to the patient’s epidermal layer through the hydrogel pad.

In a second alternative embodiment, as shown in FIG. IE, the EDP device 190 comprises a transceiver 182 having an antenna 184 for receiving signals 196, a pulse generator 187, and an electrode 183 in physical communication with a hydrogel pad. A housing 191 may be positioned around the transceiver 182, pulse generator 187, and electrode 183. In this embodiment, an external device 192 comprises the power source and controller adapted to generate an electrical signal, power signal, or data signal 196 that is wirelessly transmitted to transceiver 182 and, in turn, to the pulse generator 187 and used by the pulse generator 187 to generate a plurality of electrical pulses. The external device 192 may be a watch, mobile phone, a sensor pod configured to attach to the patient using a strap or band, or other wearable device. The electrical pulses are communicated to the electrode 183 and, thereafter, to the patient’s epidermal layer through an optional hydrogel pad.

In a third alternative embodiment, as shown in FIG. IF, the EDP device 195 comprises a transceiver 182 having an antenna 184 for receiving power signals 197, a microprocessor or

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PCT/ÜS2016/019416 microcontroller 193, a pulse generator 187, and an electrode 183 in physical communication with a hydrogel pad. A housing 194 may be positioned around the transceiver 182, microcontroller 193, pulse generator 187, and electrode 183. In this embodiment, an external device 198 comprises a power source and transceiver adapted to generate the power signal 197 that is wirelessly transmitted to the transceiver 182 of the EDP device 195 and, in turn, to the microcontroller 193 and pulse generator 187 which generates a plurality of electrical pulses. The external device 198 may be a watch, mobile phone, a sensor pod configured to attach to the patient using a strap or band, or other wearable device. The electrical pulses are communicated to the electrode 183 and, thereafter, to the patient’s epidermal layer through an optional hydrogel pad.

In a fourth alternative embodiment, each of the power source, controller, pulse generator, transceiver, electrode, and hydrogel pad are combined altogether in a single housing. In a fifth alternative embodiment, the controller, pulse generator, and/or transceiver are combined together in a first housing while the electrode, power source, and/or hydrogel pad are in a disposable second housing, thereby allowing the electrode, power source, and hydrogel to be disposed of when exhausted. Accordingly, the controller, pulse generator, and/or transceiver could be reused and connected to a second electrode, power source, and/or hydrogel pad, yielding a refreshed device.

It should be appreciated that each of the above embodiments can be implemented without a transceiver, replacing the wireless communication with a wired connection between the external device and the electro-dermal patch. It should also be appreciated that, for each embodiment, signal processing to determine data indicative of a physiological condition can be done at the sensor level, i.e. in the impedance or other sensor, at the controller level in the EDP device, or at the external device level using a mobile application software or other program.

Electro-Dermal Patch (EDP) Device Configurations

In accordance with an aspect of the present specification, the electro-dermal patch device 110 is configured as a wearable and disposable skin patch that is adhesively attached to the user’s skin with a pair of removable and replaceable conductive hydrogel pads. Alternatively, the conductive hydrogel pads are a permanent part of the electro-dermal patch device 110 and the entire assembly is disposed of once the battery depletes. The hydrogel pads provide electrical

100 continuity from the EDP device to a user’s skin surface. Hydrogel consists of a water based absorbing polymer and a water based electrolyte. Electrical current is transmitted to the skin via the electrolyte in the hydrogel. In various embodiments, both the hydrogel and the electrolyte within meet the requirements of biocompatibility as defined by ISO 10993-5,10. In some embodiments, die EDP device uses ‘foam electrodes’ with either dry or wet conductive gels applied to the center of the electrode assembly. The foam is placed along the perimeter of the electrode assembly and provides adhesion to the skin. The gel is the conductive medium between the electrode metal and the skin. The ‘foam electrodes’ are impervious to water since the foam is closed cell and acts as a barrier to water ingress to the conductive gel.

In accordance with an aspect of die present specification, the electro-dennal patch device 110 is configured to be worn for prolonged usage, such as for at least 1,2,3,4, 5, 6, 7, 8,9,10, 11,12,13,14 days or up to 3 months continuously or any increment dierein, and removed solely for the purpose of recharging and/or changing the replaceable conductive hydrogel pads. The adhesive of the pads is preferably biocompatible to prevent skin irritation due to prolonged usage of the patch. Loctite*, manufactured by Henkel, is a non-limiting example of a medical or biocompatible adhesive. The adhesive of the pads provides sufficient attachment integrity of the EDP to the user’s skin. In various embodiments, the EDP has an average minimum ‘peel strength’ in a range of 1.3 to 1.7 Newton and preferably 1.5 Newton on living skin. In one embodiment, the EDP device uses the KM30B hydrogel, manufactured by Katecho Inc., having a ‘peel strength’ in a range of 1 to 2.5 Newton. Persons of ordinary skill in the art would appreciate that ‘peel strength’ is the force required to remove or peel off the EDP, having adhesive pads, from the user’s skin and is a measure of the attachment integrity of the EDP. ‘Peel strength* is typically quantified by pulling the device from a flexible end or edge at an angle of 90 degrees from the skin surface at a peel rate that ranges from 100 to 500 mm/minute. hi alternate embodiments, placement of the electro-dermal patch device 110 is accomplished using a band, strap or a belt (for example, at the user’s arm or wrist regions). It should be appreciated that the term “adhered” is intended to encompass all forms of achieving device-to-skin contact, including adhesives, bands, straps, or belts.

In accordance with some embodiments, the one or more electrodes 118 enable Ihe electrodermal patch device 110 to provide electrical stimulation therapy, from the external surface of

101

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PCT/ÜS2016/019416 the patient’s epidermal layer through a range of 0.1 mm to 10 mm or a range of 0.1 mm to 20 mm of the dermis, to a user. In various embodiments, a stimulation depth through the patient's epidermal layer ranges from 0.1 mm to 0.5, 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mm or any increment therein. An embodiment of the present specification uses two electrodes disposed in hydrogel pads. The electrode pads are disposed on the surface of the skin of the user to pass electrical pulses through the skin and stimulate nerves and nerve endings in body tissues under the skin in the region of the electrodes.

FIGS. 2A, 2B and 2C are respectively side, front and top perspective views of an electrodermal patch device 210, in accordance with an embodiment, having a pair of conductive hydrogel pads 220 and a device housing 213. The housing 213 includes the microcontroller, pulse generator, wireless transceiver, and power management module of the system described with reference to FIG. 1 A. The electrodes extend from the housing 213 and into the pads 220 for placement proximate the skin surface of a patient. In one embodiment, the pads 220 have at least one and preferably two electrodes (not shown) disposed or printed on a lower surface 222 of the pads 220. The pads 220, when adhered to a user’s skin, enable the electrodes to be in direct contact with the outer surface of the skin. In various embodiments, the electrodes can be in the form of typical gel-based skin electrodes, gel-less skin electrodes, or skin puncturing or skin abrading electrodes in order to reduce skin-electrode impedance. In various embodiments, the electrode surface area ranges from 0.1 inches2 to 10 inches2, 0.001 inches2 to 0.1 inches2, or 0.001 inches2 to 10 inches2.

In some embodiments, hydrogel pads 220 of the electro-dermal patch device of the present specification are replaceable, enabling re-attachability of new conductive pads and therefore new adhesion surfaces to the EDP device. FIG. 2D is an oblique perspective view of an electro-dermal patch 230 with hydrogel removed and a replacement hydrogel 240 with liners 242, 243, in accordance with one embodiment of the present specification In accordance with an aspect of the present specification, used hydrogel pads can be peeled off the EDP device by pulling on a removal tab 241. In one embodiment, the removal tab 241 is made from a white polyester film. On one side of this film there is an acrylic adhesive. When building the hydrogel and removal tab assembly, the acrylic side is placed facing the hydrogel on both the top and bottom. The replacement pad 240 is a custom shaped hydrogel, sandwiched between two pieces of transparent release liners 242,243, in accordance with an embodiment. An EDP-facing release

102

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PCT/ÜS2016/019416 liner 242 is peeled away. The second piece of release liner 243, facing a skin surface, is used to handle and locate the hydrogel 240 accurately onto the bottom of the EDP 230. Light finger pressure is applied through the second release liner 243 to insure good contact to the EDP 230. The second liner 243 is then peeled away thus exposing the working surface of the hydrogel.

In an alternate embodiment, referring again to FIGS. 2A-2C, the housing 213 is detachable from the hydrogel pads 220 and can be snap-connected to the hydrogel pads 220.

The skin patches or pads 220 can have different shapes and sizes for different body types and areas of stimulation. In some embodiments, the patches or pads are irregularly shaped. In various embodiments, the patches or pads 220 are rectangular having a length of about 2 inches, a breadth of about 1 inches and a thickness of about 0.2 inches. In another embodiment, the patches or pads 220 are rectangular having a length of about 3 to 5 inches, a breadth of about 0.5 to 2.5 inches and a thickness of about 0.10 - 0.30 inches. In various other embodiments, the patches or pads 220 are round or circular having a diameter of about 2 to 4 inches and a thickness of about 0.10 to 0.30 inches. In still other embodiments, the patches or pads 220 are square having sides of about 2 to 4 inches and a thickness of about 0.10 to 0.30 inches. The patches or pads 220 can have other sizes and shapes such as, but not limited to, elliptical or triangular. In other embodiments, the electrode/pad combination may have a shape including any one of irregular, rectangular, circular, square, elliptical, and triangular and wherein, at its widest, would between 0.25 to 5 inches in width, at its tallest would be between 0.25 to 5 inches in height, and at its thickest would be between 0.25 to 5 inches in thickness. In another embodiment, the device would comprise two of such electrode/pad combinations placed side by side.

In accordance with various embodiments, the electrodes are disposed or printed on the lower surface 222 of the pads 220 in the form of a plurality of patterns or geometries. FIGS. 3A and 3B illustrate, respectively, a first pattern 305 and a second pattern 310 of first 318, 318’ and second electrodes 328, 328’. Referring to FIG. 3 A, in one embodiment, the electrodes 318, 318’ each have a ‘comb’ like pattern comprising an elongate ‘backbone’ 319, 319’ with a plurality of ‘teeth’ 317, 317’ extending perpendicularly therefrom. The two electrodes 318, 318’ are positioned facing one another such that the ‘teeth’ 317 of a first electrode 318 are configured to alternate between the ‘teeth’ 317’ of a second electrode 318’. Referring to FIG. 3B, in one embodiment, the electrodes 328, 328’ each have a ‘square wave’ pattern comprising a plurality

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PCT/ÜS2016/019416 battery, and a flexible overmold 435. In a less preferred embodiment, the controller assembly comprises a rigid housing in place of the overmold. In some embodiments, the overmold 435 comprises a low durometer material with its geometry defined via a single shot injection mold process wherein there is one durometer throughout the entire overmold 435.

In various embodiments, materials for the overmold 435 include a thermoplastic elastomer, or (TPE), such as, for example, Monprene manufactured by Teknor Apex as an ultrasoft TPE gel. TPEs are processed like any other thermoplastic material but typically have low elastic moduli, thus making the assembly flexible. In various embodiments, the TPE used as material for the overmold 435 has hardness in a range of 30 to 70, preferably 45-65, and more preferably 50 to 60 on the sub-zero shore (00) scale and a tensile modulus (indicative of flexural properties) in a range of 15 to 55 psi, preferably 30 to 45 psi. For example, Monprene Ultra Soft Gel grade CP-32053G (manufactured by Teknor Apex) has a hardness measure of 53 on the subzero shore (00) scale and a tensile modulus of about 37 psi. Viscosity of the Monprene Ultra Soft Gel ranges from 30 to 65 on the subzero shore (00) scale. The EDP device of the present specification, taken as a whole, has a measurement on the flexural modulus scale per ASTM D747 in a range of lOpsi to 35psi, preferably 15 to 25psi. Such overmolding material applies to all other embodiments disclosed herein, whether in a single shot or dual shot molding embodiment.

PCT/ÜS2016/019416

Once the EDP is fully assembled, the electrode contacts 439 depicted in FIG. 4F are in physical contact with the hydrogel 436 depicted in FIG. 41 to allow for transmission of electrical stimuli from the EDP to the skin surface of a patient. The hydrogel carrier 438 and release liner 442 allow for simple separation of the controller assembly from the electrode assembly 432 so that a reusable controller assembly can be joined with a new electrode assembly.

FIG. 41 is an oblique, bottom perspective view of the electro-dermal patch device 430 of FIG. 4D. Visible are the overmold 433 and flexible circuit carrier 437 of the controller assembly and the hydrogel 436, hydrogel carrier 438, and electrode bezel 434 of the electrode assembly.

FIG. 4K is a side perspective view of the electro-dermal patch device 430 of FIG. 4D. In various embodiments, the EDP 430 has a thickness, or height h from a patient’s skin surface, in a range of 0.075 to 0.25 inches. In one embodiment, the EDP 430 has a thickness, or height h from a patient’s skin surface of 0.156 inches.

FIGS. 4L and 4M are oblique, top perspective, short axis and front perspective, crosssectional views respectively, of the electro-dermal patch device 430 of FIG. 4D. Visible are the overmold 435, discrete component 445, battery 447, flexible circuit carrier 437, and circuit carrier anchor 443 of the controller assembly 431 and the hydrogel 436, hydrogel carrier 438, and electrode bezel 434 of the electrode assembly 432. The controller assembly 431 is configured to detachably connect to the electrode assembly 432 such that the overmold 435 sits within an area defined by the electrode bezel 434 and the electrode contacts (439 in FIG. 4F) are in physical contact with the hydrogel 436. Using a patient’s skin surface as a point of reference, the overmold 435 of the controller assembly 431 and the electrode bezel 434 of the electrode assembly 432 comprise a distal or outer surface 430d of the EDP 430. The hydrogel 436 comprises a proximal or inner, skin facing surface 430p of the EDP. The discrete component 445, battery 447, flexible circuit carrier 437, and circuit carrier anchor 443 are positioned within the controller assembly 431 in a central portion of the EDP 430. The hydrogel carrier 438 is positioned between the electrode bezel 434 and hydrogel 436 of the electrode assembly 432 about a periphery of the EDP 430.

FIGS. 4N and 40 are oblique, top perspective, long axis and side perspective, crosssectional views respectively, of the electro-dermal patch device 430 of FIG. 4D. Visible are the overmold 435, discrete component 445, battery 447, flexible circuit carrier 437, circuit carrier

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PCT/ÜS2016/019416 anchor 443, and slots 433 of the controller assembly 431 and the hydrogel 436 (seen in FIG. 40), hydrogel carrier 438, and electrode bezel 434 of the electrode assembly 432.

PCT/ÜS2016/019416 saturated olefin polymer. The higher durometer material ranges from 35 to 45 Shore A, in various embodiments, with the lower durometer material being below 35 Shore A.

In various embodiments, the electro-dermal patch device 500 has an ingress protection rating (IPX) of at least IPX7, allowing the patient to take showers and swim for at least 30 minutes while the electro-dermal patch device 500 is positioned on the body without water damage to the electro-dermal patch device 500. In various alternate embodiments, the EDP device 500 has an ingress protection rating (IP) ranging from IP3 to IP5 and preferably a waterproof rating of IP4 (that is, protection from water splashing from any direction for 5 minutes) per EEC standard 60529.

In various embodiments, the flexible overmold, such as the overmold 435 of FIG. 4E and the overmold 515 of FIG. 5A, is also non-toxic to safeguard against any incidental contact with the skin.

In various embodiments, the housing 530 has a typical footprint area of 1.5 inches2 for a physical aspect ratio of the width to the length of the flexible circuit carrier 525 of about 1:1.

In one embodiment, the electro-dermal patch device (EDP) comprises a print-on-the-skin circuit designed to be printed directly onto the epidermis of a patient. The printable EDP comprises film electrodes having a thickness sufficient to withstand the currents required for the electrical stimulation protocols of the current specification without degrading. The printable EDP comprises a wireless transceiver (for communication with a companion device), microcontroller, power management module or battery, pulse generator, and at least one electrode. In some embodiments, the printable EDP further includes at least one sensor.

In another embodiment, the electro-dermal patch device (EDP) comprises a highly flexible membrane, or ‘flex-circuit’, configured to adhere to the patient’s epidermis. The ‘flexcircuit’ is configured to be applied and adhere to the patient’s skin much like a conventional tattoo. The ‘flex-circuit’ comprises a curved, or‘S* shaped circuit. The curved shape allows the ‘flex-circuit’ to move with the patient’s skin without being damaged. The ‘flex-circuit’ EDP comprises a wireless transceiver (for communication with a companion device), microcontroller, power management module or battery, pulse generator, and at least one electrode. In some embodiments, the ‘flex-circuit’ EDP further includes at least one sensor.

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In yet another embodiment, the electro-dermal patch device (EDP) comprises a combination of a printed circuit board, for example grade FR-4, and a flex circuit, for example Kapton®, with a connector.

In various embodiments, the dimensions and/or form factor of the electro-dermal patch device of the present specification has any one or a combination of the following attributes: at least one dimension of length or width measuring less than 1.26 inches; a volume in a range of 0.25 inches3 to 0.5 inches3; a weight in a range of 15 grams to 80 grams; a physical aspect ratio of width to thickness in a range of 1:1 to 6:1; a footprint of the EDP device in a range of 3.5 inches2 (1:1 aspect ratio) to 6 inches2 (6:1 aspect ratio); an electrical aspect ratio in a range of 1:1 to 1.5:1. In various embodiments, a ratio of EDP electrode surface area to EDP weight is selected to keep the size of the electrode equal to or smaller than the skin contacting foot print of the EDP device. In some embodiments, the ratio of EDP electrode surface area to EDP weight is in a range of 0.1 to 0.8 square inches per gram weight of the EDP device, preferably between 0.2 and 0.5 in2/gram.

In some embodiments, a substantially rectangular shaped EDP (such as that of FIGS. 4B, 4C) has a width of 1.25 inches, a length of 4.0 inches and a height of 0.15 inches. In some embodiments, a circular shaped EDP (such as that of FIGS. 5 A through 5F) has a radius of 1.125 inches and a height of 0.15 inches.

It should be appreciated that, while different physical configurations may exist for the electrical dermal patch, it is important that the device deliver enough electrical stimulation in a reasonably sized patch structure, namely one that is not so large that it would be uncomfortable to wear. To that end, in one embodiment, a preferred electrical dermal patch comprises an electrode that is removably attached to the surface of the housing. The contact surface area of such electrode is in a range of O.lin2 to 10in2, or, more preferably, 0.5in2 to 4in2 and the programmable current ranges from ΙΟΟμΑ to 500mA, or, more preferably, 2mA to 50mA. In these embodiments, the current density of the electrical dermal patch is in a range of ΙΟμΑ/in2 to 5000mA/in2, more preferably 25μΑ/ΐη2 to 1000mA/in2, and even more preferably 0.5mA/in2 to lOOmA/in2. The total contact surface area of the electrical dermal patch in this configuration is equal to the contact surface area of its electrode(s).

In another embodiment, a preferred electrical dermal patch comprises an electrode that is at least partially affixed within the housing and not removably attached to a surface of the

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PCT/ÜS2016/019416 housing. The contact surface area of such electrode is in a range of 0.1 in2 to 10in2, or, more preferably, 0.5in2 to 4in2 and the programmable current ranges from ΙΟΟμΑ to 500mA, or, more preferably, 2mA to 50mA. In these embodiments, die current density of the electrical dermal patch is in a range of ΙΟμΑ/ίη2 to 5000mA/in2, more preferably 25pA/in2 to lOOOmA/in2, and even more preferably 0.5mA/in2 to 100mA/in2. The total contact surface area of the electrical dermal patch in this configuration is equal to the contact surface area of its electrode(s) plus a small additional amount for peripheral portions of the housing, which typically will not amount to more than an additional 5-10% more contact surface area relative to the electrode(s) surface area.

It should be appreciated that, in either configuration, one, two, three or more electrodes may be attached to the housing, or integrated into the housing, each having the characteristics described above, without departing from the scope of this invention.

Companion Device/Control

Referring back to FIG. 1 A, the electro-dermal patch device 110 is in data communication with and controlled by the companion device 105 in accordance with an aspect of the present specification. The companion device 105 is further capable of being in data communication with a remote patient care facility and/or patient care personnel. The companion device 105 is in data communication with the electro-dermal patch device 110 through a direct link to drive therapy. In accordance with a preferred embodiment, the companion device 105 is a hand-held computing device such as a watch, wristband, smartphone, tablet, or PDA that controls the electro-dermal patch device 110 through a wireless connection, such as Bluetooth, WiFi or any other private/public cellular or TCP/IP network such as the Internet. In some embodiments, the companion device is physically separated from and external to the EDP, hence referred to as a separate or external device. In some embodiments, the companion device may be a wearable activity monitor that tracks heart rates, movement, and other physiological data. In some embodiments, the EDP may be integrated into a wearable activity monitor and communicate with an external device, such as a smartphone, that is executing a software application in data communication with the wearable activity monitor.

The companion device 105 is configured to monitor and record (‘leam’) a patient’s appetite patterns and monitor and record, leam, and modify the stimulation parameters of the

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PCT/ÜS2016/019416 stimulation protocols delivered by the electro-dermal patch device 110. In some embodiments, all therapy provided by the electro-dermal patch device 110 is coupled with recording (keeping a log of the therapy) and patient compliance reminders provided by the companion device 105. FIG. 6A shows the electro-dermal patch device 610 of the present specification, configured as a skin patch and placed at a lateral thoracic dermatome, in accordance with an embodiment, and being wirelessly controlled by a smartphone 605, for example.

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PCT/ÜS2016/019416 stimulation settings, and a modulation signal is transmitted in order to establish those new (optimum) stimulation settings.

In various embodiments, the EDP device, and the electrical stimulation it delivers, is configurable and re-configurable for different therapies and for different aspects within a specific therapy. For example, regarding weight loss and management, the patient and/or companion device can configure the EDP to deliver electrical stimulation in an effort to promote active weight loss in the patient and then, once a target weight is achieved, reconfigure the EDP to deliver electrical stimulation to maintain the patient at the target weight. This can be accomplished via one or more applications downloaded to the companion device. FIG. 6D is a flow chart illustrating the steps involved in using one or more downloadable applications to configure and reconfigure stimulation provided by an electro-dermal patch (EDP) device, in accordance with one embodiment of the present specification. At step 680, a patient obtains an EDP from a medical professional. At step 681, the patient pairs a companion device with the EDP and with a separate physiological monitoring device with physiological sensors, configured to be worn on the human body, such as around the wrist, in order to monitor, acquire, record, and/or transmit physiological data to the companion device, wherein the companion device is adapted to create and modify stimulation parameters based on the monitored physiological data. At step 682, the patient then downloads, from an online marketplace, a first application designed to configure the EDP to achieve a first objective associated with a specific therapy, for example, weight loss for weight management. The patient positions the EDP on his body at step 683. The first application, at step 684, configures the EDP for the first objective by establishing certain baseline stimulation parameters designed to achieve said first objective and by titrating or finetuning said stimulation parameters based on patient diary input into the companion device and/or physiological data transmitted to the companion device by the separate monitoring device. After the first objective has been achieved, at step 685, the patient then downloads a second application, from an online marketplace, designed to reconfigure the EDP to achieve a second objective associated with the specific therapy, for example, maintaining weight for weight management.

In various embodiments, one or both of the first and second applications is available from the online marketplace for a fee. Additionally, both the first and second applications may be separate and distinct applications which reside on the companion device, are separately obtained

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PCT/ÜS2016/019416 by accessing the on-line application marketplace associated with the companion device, and are activated, and executed, by clicking on separate and distinct icons from the companion device’s home screen. In another embodiment, the first application may be downloaded from the on-line application marketplace associated with the companion device and may be activated, and executed, by clicking on separate and distinct icons from the companion device’s home screen while the second application, and all subsequent applications responsible for modulating the EDP’s stimulation parameters, are downloaded by accessing a marketplace of such applications through the first application. Specifically, the first application provides a gateway to a database, or library, of additional applications which may provide for different stimulation parameters based on inputs, weights, and other criteria that differ from the first application, or each other.

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PCT/ÜS2016/019416 between the EDP and companion device, and/or between the companion device and remote servers) are encrypted, authenticated, and anonymized subject to verification. In another case, only data transmissions containing patient-specific stimulation settings or patient status data are encrypted, authenticated, and/or subject to verification while all other data transmissions are not encrypted.

If, on the other hand, the companion device or remote servers) determines the EDP in question is not subject to FDA approval (based on an identifier being stored in a memory within the EDP), it may cause a lower level of encryption, authentication, and/or verification to be applied to the stored data or to data transmissions relative to the FDA case. In one embodiment, no data transmissions to and from the EDP, between the EDP and companion device, and/or between the companion device and remote servers) are encrypted, authenticated, and subject to verification. In another case, only data transmissions containing patient-specific stimulation settings or patient status data are authenticated and/or subject to verification and no data transmissions are encrypted.

Figure 6F is a flow chart illustrating the steps involved in a method of encrypting, authenticating, and/or verifying data transmissions between an EDP, companion device, and remote server based on FDA approval status of the EDP, in accordance with some embodiments of the present specification. At step 661, a patient obtains an electro-dermal patch (EDP) device from a medical professional. The patient pairs a companion device with the EDP and with a remote server, in a secure manner subject to verification and authentication, at step 662. At step 663, the companion device and/or remote server determine if the EDP is subject to FDA approval based on an indication (packet header, identifier, tag) on the EDP. In one embodiment, if it is determined that the EDP is subject to FDA approval, then all data transmissions to and from the EDP, between the EDP and companion device, and/or between the companion device and remote server are encrypted, authenticated, and subject to verification at step 664. hi another embodiment, at step 666, if it is determined that the EDP is subject to FDA approval, only data transmissions containing patient-specific stimulation settings or patient status to and from the EDP, between the EDP and companion device, and/or between the companion device and remote server are encrypted, authenticated, and/or subject to verification and all other data transmissions are not encrypted. In another embodiment, if it is determined that the EDP is not subject to FDA approval, then no data transmissions to and from the EDP, between the EDP and companion

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PCT/ÜS2016/019416 device, and/or between the companion device and remote server are encrypted, authenticated, and subject to verification at step 667. In another embodiment, at step 669, if it is determined that the EDP is not subject to FDA approval, only data transmissions containing patient-specific stimulation settings or patient status to and from the EDP, between the EDP and companion device, and/or between the companion device and remote server are authenticated and/or subject to verification and no data transmissions are encrypted.

In accordance with an aspect of the present specification, patient status data and, if needed, stimulation setting, parameters and protocols are transmitted to insurance companies to support medical treatments, such as bariatric surgeries, or other insurance claims, or for other general insurance data needs. In some embodiments, such data transmission may be subjected to encryption, authentication and verification as described at step 666.

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PCT/ÜS2016/019416 device, with physiological sensors, configured to be worn on the human body, such as around the wrist, in order to monitor, acquire, record, and/or transmit the physiological data.

The HMA enables presenting GUI screens to enable the user to provide inputs such as, but not limited to, eating information and activities information. In various embodiments, eating information comprises standard regular eating and meals profile or routine of the user such as the number of meals per day typically consumed and the types and amounts of food eaten at each of the meals per day. The standard regular eating and meals profile is typically input only once by the user as it represents the general eating habit of the user and is likely to be modified by the user over long periods of time. In some embodiments, the standard regular eating and meals profile is representative of a standard diet plan such as, but not limited to, Mediterranean, Intermittent Fasting, Jenny Craig, Weight Watchers, SlimFast and Custom Plan.

In various embodiments, eating information additionally or alternatively comprises real time actual eating and meals profile of the user such as the time of consumption of a meal in a day and the type and amount of food eaten at the meal. In other words, each time the user consumes a meal he (in real time) records the occurrence of the meal event, which is automatically time stamped by the application, as well as the type and amount of food eaten. If the meal being consumed and the type and amount of food are in line with the user’s standard regular eating profile, he may simply select the meal and types and amounts of food from the pre-stored eating profile of the user.

In accordance with an aspect of the present specification, the real time eating and meals profile is utilized to calculate the actual amount of calories consumed by the user in a day. On the other hand, the standard regular eating and meals routine of the user is utilized to calculate a forecasted or expected amount of calories likely to be consumed by the user in a day. A difference between the daily, weekly or monthly expected and actual calories consumption value may prompt a plurality of recommendations from the Health Management application to the user.

In accordance with some aspects of the present specification, it is advantageous to also assess the quality of meal or diet consumed along with the amount of calories consumed as a result of the meal or diet in a day. In some embodiments, the quality of a meal or diet is determined based on a mix of macronutrients such as carbohydrates (also referred to as “carbs”), proteins and fats present in the meal or diet. Thus, the user’s standard diet plan may propose an acceptable ratio for each macronutrient. For example, the Zone Diet (by Barry Sears, PhD)

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The HMA enables managing and generating prompts (audio, visual and/or tactile) with respect to a plurality of compliance aspects such as, but not limited to: stimulation therapy

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PCT/ÜS2016/019416 compliance - prompts the user if the user forgets to apply the electro-dermal patch device and/or disables a recommended duration or frequency of stimulation therapy; prompts the user with respect to a stimulation protocol that a scheduled stimulation is going to begin in the next T minutes, 10 minutes for example, and presenting the user with an option to disable the scheduled stimulation which if not disabled allows the scheduled stimulation to begin after T minutes; dietary compliance or guidance - the user either selects a predefined standard dietary plan (from a drop down list of multiple predefined dietary plans, such as but not limited to Mediterranean Zone diet, Atkins diet, or Jenny Craig) or inputs a customized plan as part of the standard regular eating and meals routine. The user also records details of the actual meals taken and time of meals. Audio, visual and/or tactile alert(s) may be generated, for example, if the user is not in compliance with the selected dietary plan. The compliance prompts are intended to encourage patient compliance and, in some embodiments, include composite scores and displays for overall patient progress.

The HMA enables recommending and/or implementing modification to stimulation patterns or protocols when receiving an input from the user that the user is encountering a feeling of nausea, dyspepsia, heartbum, or sensation at the stimulation site during and/or after stimulation.

The HMA further enables assessing stimulation habituation, nausea and/or dyspepsia scenarios in the user and accordingly modifying the stimulation patterns or protocols. In various embodiments, these events are input into the electro-dermal patch device or companion device by the patient. For example, in one embodiment, the patient can input, via a GUI on one or both devices, nausea events, dyspepsia events or hunger events. The microprocessor then algorithmically processes these events and accordingly modifies stimulation.

The HMA enables the remote patient care facility and/or patient care personnel to access (via cellular and/or private or public wired or wireless networks such as the Internet) a plurality of user’s health related information such as the user’s hunger profile, standard eating and meals profile, actual eating and meals profile, energy balance, weight trends, glucose data and stimulation induced nausea, dyspepsia, habituation events. In some embodiments, the Health Management application periodically transmits the user’s health related information apart from enabling the remote patient care facility and/or patient care personnel to access such information

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PCT/ÜS2016/019416 in real time or on demand, if required. In various embodiments, the user’s authorization is needed to allow such access to the user’s health related information.

The HMA also enables detecting removal of the electro-dermal patch device - the impedance or bio-impedance electrode enables the Health Management application to regularly or continuously monitor electrode and skin contact impedance. This allows the Health Management application to detect whether the electro-dermal patch device has been removed or worn by the user. In some embodiments, where the electro-dermal patch device is configured for use as a 24/7 wearable device, detection of removal of the electro-dermal patch device corresponds to missing of the user’s health related information. However, in other embodiments, where the electro-dermal patch device is configured for use on as-needed or on-demand basis, any missing user health related information is treated as non-occurrence of any stimulation event.

The HMA also enables providing unique electrical stimulation characteristics and ‘footprints’, based on electrode design and stimulation parameters, allowing the patient to use a variety of methodologies for stimulation.

In still a further non-limiting example, the HMA enables providing a weight loss graph along with the patient’s pictures corresponding to various milestones on the weight loss graph.

In still a further non-limiting example, the HMA enables; enables bariatric surgeons, doctors, dieticians or medical personnel to tell new patients about their medical practice.

In still a further non-limiting example, the HMA enables patients to keep time intervals between meals and fluids. For example, the HMA may notify users when enough time has passed after drinking to eat and vice versa.

In still further non-limiting examples, the HMA enables patients to view their medical personnel and request an appointment with the office; enables setting of daily reminders for prescribed vitamins and supplements; enables patients to pose queries to their dietician; enables communicating schedules of weight loss seminars and support groups, to the patients; enables medical personnel to communicate healthy recipes with the patients to support their continued weight loss success; enables bariatric surgery patients to stay on track with reminders and a prepopulated checklist - Psych Eval, Insurance Pre-approval, Physician Supervised Diet; enables medical personnel as well as patients to journalize daily thoughts and progress notes; enables information exchange with third party applications; enables patients to track their water intake along with food consumed; enables automatic tracking of calories, protein, fat and carbohydrates

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PCT/ÜS2016/019416 consumed by patients; enables scanning of barcodes of package food to allow patients to see the nutritional information, and have it logged automatically to the feed consumed daily diary; enables physicians or medical personnel to enter specific goals for their patients; enables physicians to share their patient status data, with approval from their patients, with the fellow practice/department physicians to solicit better recommendations for the patients; enables instilling weight management habits in the patients since monitoring of food/calories intake leads to better dietary compliance; enables physicians, dieticians and other medical personnel to send out push notifications to their patients to keep the patients engaged and motivated towards their health goals.

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FIG. 12 is a screen shot of a companion device depicting an exercise entry screen 1205, in accordance with one embodiment of the present specification. The exercise entry screen 1205 allows the user to enter the type 1206 and item 1207 of patient parameter, in this case exercise, and a score 1208 associated with the parameter. The score 1208 has a numerical value 1209 and a description 1210 associated therewith to help the patient determine which score best fits the current parameter. In some embodiments, for exercise, the description relates to how many steps the patient took per day. In some embodiments, the score ranges from 1 to 5. The exercise entry screen 1205 also displays the time and date 1203 the entry is being entered and the name of the diary 1202. The patient can save the entry by pressing the disk icon 1201 or cancel the entry by pressing the X icon 1204.

FIG. 13 is a screen shot of a companion device depicting a hunger entry screen 1305, in accordance with one embodiment of the present specification. The hunger entry screen 1305 allows the user to enter the type 1306 and item 1307 of patient parameter, in this case hunger, and a score 1308 associated with the parameter. The score 1308 has a numerical value 1309 and a description 1310 associated therewith to help the patient determine which score best fits the current parameter. In some embodiments, for hunger, the description relates to the level of hunger the patient is experiencing. In some embodiments, the score ranges from 1 to 5. The hunger entry screen 1305 also displays the time and date 1303 the entry is being entered and the name of the diary 1302. The patient can save the entry by pressing the disk icon 1301 or cancel the entry by pressing the X icon 1304.

FIG. 14 is a screen shot of a companion device depicting a stimulation session entry screen 1405, in accordance with one embodiment of the present specification. The stimulation session entry screen 1405 allows the user to enter the type 1406 and item 1407 of session, in this case a stimulation session, and a level 1408 associated with the session. The level 1408 has a numerical value 1409 and a description 1410 associated therewith to help the patient determine which level best represents what was applied during the current session, hi some embodiments, for stimulation session, the description relates to how often stimulation was delivered per day and for how long the stimulation was applied during each session. In some embodiments, the level ranges from 1 to 4. The stimulation session entry screen 1405 also displays the time and date 1403 the entry is being entered and the name of the diary 1402. The patient can save the entry by pressing the disk icon 1401 or cancel the entry by pressing the X icon 1404.

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PCT/ÜS2016/019416 dermatomes in the hand and arm along with the front (anterior) C5 - T1 dermatomes on the upper chest region (hereinafter together referred to as ‘hand dermatomes’). In various embodiments, the ‘area of interest’ expressly excludes the back (posterior) C5 - T1 dermatomes of the upper chest region since the back portions are inaccessible to the user and therefore would need a medical practitioner to apply the devices of the present specification.

In some embodiments, the ‘area of interest’ comprises at least one of the patient’s T2 frontal and lateral thoracic dermatome, T3 frontal and lateral thoracic dermatome, T4 frontal and lateral thoracic dermatome, T5 frontal and lateral thoracic dermatome, T6 frontal and lateral thoracic dermatome, T7 frontal and lateral thoracic dermatome, T8 frontal and lateral thoracic dermatome, T9 frontal and lateral thoracic dermatome, and T10 frontal and lateral thoracic dermatome and does not include any one of the patient’s T2 posterior thoracic dermatome, T3 posterior thoracic dermatome, T4 posterior thoracic dermatome, T5 posterior thoracic dermatome, T6 posterior thoracic dermatome, T7 posterior thoracic dermatome, T8 posterior thoracic dermatome, T9 posterior thoracic dermatome, and T10 posterior thoracic dermatome.

In some embodiments, the ‘area of interest’ comprises at least one of the patient’s C8 anterior or posterior dermatome located on the patient’s hand, wrist, elbow, and fingers, C8 anterior or posterior dermatome located on the patient’s arm, C8 dermatome located on the patient’s upper trunk, T1 anterior or posterior dermatome located on the patient’s arm, T1 anterior or posterior dermatome located on the patient’s wrist, elbow, and hand, and T1 anterior or posterior dermatome located on the patient’s upper trunk.

In some embodiments, the ‘area of interest’ comprises at least one of the patient’s C5, C6, C7, C8, Tl, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, and T12 dermatomes.

In some embodiments, the ‘area of interest’ comprises at least one of the patient’s C5, C6, C7, C8, Tl, T2, T3, T4, T5, T6, T7, T8, T9, T10, Til, and T12 frontal and lateral dermatomes

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PCT/ÜS2016/019416 and does not include any portion of the patient’s C5, C6, C7, C8, Tl, T2, T3, T4, T5, T6, T7, T8, T9, T10, Til, and T12 posterior dermatomes.

In alternate yet less preferred embodiments, the ‘area of interest’ comprises one or more meridians.

FIG. 17A is an illustration depicting the distribution 1700 of the front and lateral, or frontal, T2 - T12 dermatomes across a thorax and abdomen, that is trunk, of a human body. The frontal dermatome is defined as the front and lateral thoracic dermatome which expressly do not include die back or spinal roots of said patient. In various embodiments, the electro-dermal patch devices of the present specification are positioned on the surface of the epidermis on the front portion 1702 or lateral portion 1704 of the T2 - T12 dermatomes. The electrode(s) positioned in the pads or skin patches of the electro-dermal patch device then provide electrical stimulation to the epidermis of the targeted dermatome(s). The T2 to T12 dermatomes are anatomically identifiable as follows:

T2 - At the apex of the axilla.

T3 - Intersection of the midclavicular line and the third intercostal space.

T4 - Intersection of the midclavicular line and the fourth intercostal space, located at the level of the nipples.

T5 - Intersection of the midclavicular line and the fifth intercostal space, horizontally located midway between the level of the nipples and the level of the xiphoid process.

T6 - Intersection of the midclavicular line and the horizontal level of the xiphoid process.

T7 - Intersection of the midclavicular line and the horizontal level at one quarter the distance between the level of the xiphoid process and the level of the umbilicus.

T8 - Intersection of the midclavicular line and the horizontal level at one half the distance between the level of the xiphoid process and the level of the umbilicus.

T9 - Intersection of the midclavicular line and the horizontal level at three quarters of the distance between the level of the xiphoid process and the level of the umbilicus.

T10 - Intersection of the midclavicular line, at the horizontal level of the umbilicus.

Til- Intersection of the midclavicular line, at the horizontal level midway between the level of the umbilicus and the inguinal ligament.

T12 - Intersection of the midclavicular line and the midpoint of the inguinal ligament.

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FIG. 17B is an illustration depicting the distribution 1701 of the front and back, C5 - T1 dermatomes across the hand 1705, arm 1710 and upper chest 1715 regions of a human body. In various embodiments, the electro-dermal patch devices of the present specification are positioned on the surface of the epidermis on the front portion 1720 and/or back portion 1725 of the C5 T1 dermatomes on the hand 1705 and arm 1710 along with the front (anterior) C5 - T1 dermatomes on the upper chest 1715. FIG. 17C is an illustration depicting the distribution of the C5 - T1 dermatomes across the hand 1705 and lower arm 1711 regions. In various embodiments, the electro-dermal patch devices of the present specification are positioned on the surface of the epidermis on the front (palm) and/or back side of the hand 1705 targeting the C6 - C8 dermatomes or on the front and/or back side of the lower arm 1711 (such as at a wrist region, for example) targeting the C5 and T1 dermatomes. The electrode(s) positioned in the pads or skin patches of the device then provide electrical stimulation to the epidermis of the targeted dermatome(s).

The C5 - T1 dermatomes are anatomically identifiable as follows:

C5 - On the lateral (radial) side of the antecubital fossa, just proximally to the elbow.

C6 - On the dorsal surface of the proximal phalanx of the thumb.

C7 - On the dorsal surface of the proximal phalanx of the middle finger.

C8 - On the dorsal surface of the proximal phalanx of the little finger.

T1 - On the medial (ulnar) side of the antecubital fossa, just proximally to the medial epicondyle of the humerus.

FIG. 17D is a flow chart listing the steps involved in one method of identifying a proper placement location for an electro-dermal patch on a front thoracic surface of a patient, in accordance with one embodiment of the present specification. At step 1732, the patient, a physician, or anyone placing the EDP device on the patient, finds a midclavicular line of the patient. The person applying the device then progresses downward from the midclavicular line to a bottom rib of a thoracic cage of the patient at step 1734. From the bottom rib, at step 1736, the person applying the device moves downward by 2 cm to identify a placement spot. At step 1738, the person applying the device places a top center portion of the electro-dermal patch at the placement spot.

Referring back to FIG. 1A, in various embodiments, at least one thoracic dermatome, from T2 to T12 and/or ‘arm dermatome’ or ‘hand dermatome’ C5-T1, is stimulated by the

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PCT/ÜS2016/019416 toy 2505 may take any form such as, but not limited to, a ball (as shown in FIG. 25), a cylinder, an egg shaped toy or any other squeezable toy that can be held within the patient’s hand and squeezed or compressed. As shown in FIG. 25, the squeezable toy 2505 has an outer surface 2515 that contacts the patient’s skin when the toy 2505 is held in the hand by the patient, hi various embodiments, at least one EDP device 2500 is located on the outer surface 2515 such that one or more electrodes 2518 of the EDP device contact the patient’s skin when the toy 2505 is held in hand by the patient. Alternatively, the at least one EDP device 2500 may be placed within the toy 2505 such that one or more electrodes 2518 of die EDP device are exposed through the outer surface 2515 of the toy 2505 for contact with the patient’s skin when the toy 2505 is held in hand by the patient. In accordance with an aspect of the present specification, the toy 2505 is held in the hand by the patient. The one or more electrodes 2518 contact the C8 dermatome of the patient’s palm or ventral side of the hand. In one embodiment, the region exposing the electrodes 2518 on the toy 2505 is marked or tattooed indicating that the patient should hold the toy 2505 such that the mark/tattoo contacts the regions corresponding to the C8 dermatome.

In some embodiments, the one or more electrodes 2518 deliver stimulation when the toy 2505 is squeezed or compressed by the patient but switch off the stimulation when the toy 2505 is relaxed or uncompressed by the patient. Thus, repeated compression and relaxation of the squeezable toy 2505 results in repeated cycles of stimulation and non-stimulation of the C8 dermatome. In other embodiments, the one or more electrodes 2518 initiate stimulation when the toy 2505 is squeezed the first time and thereafter continue stimulation according to a preprogrammed stimulation protocol while the patient holds the toy 2505 in his hand. In still other embodiments, the one or more electrodes 2518 initiate a pre-programmed stimulation protocol when the toy 2505 is held in the hand by the patient (without being compressed or squeezed). Thereafter, the patient may continue to squeeze the toy 2505 periodically without affecting the application of the stimulation protocol.

FIG. 26 shows still another embodiment where the EDP device is configured in the form of a hand or palm gear 2605. The hand gear 2605 comprises a housing 2611 having an upper or outer surface 2615 that includes a GUI display, for example, and a lower or inner surface (not visible) that touches the patient’s skin on the dorsal side of the patient’s hand 2606 when worn. A plurality of arms 2620 extend from the housing 2611 to enable the hand gear 2605 to be worn

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PCT/ÜS2016/019416 and held on the patient’s hand 2606 as shown in FIG. 26. In various embodiments, the EDP device (not visible) is positioned within the housing 2611 such that the one or more electrodes of the EDP device are exposed through the lower or inner surface of the housing 2611 to enable contact with the patient’s skin (on the dorsal side of the patient’s hand 2606) when worn, hi accordance with an embodiment, the one or more electrodes stimulate the C8 dermatome on the patient’s dorsal side of the hand 2606.

Thus, in accordance with some aspects of the present specification, electrical stimulation from the external surface of the patient’s epidermal layer through 10 mm or 20 mm of the dermis (using the electro-dermal patch device 110 of FIG. 1A) provides for a non-invasive treatment of appetite suppression, ghrelin production modulation, eating disorders, excessive weight or overweight, obesity, metabolic syndrome and diabetes. In various embodiments, a stimulation depth through the patient's epidermal layer ranges from 0.1 mm to 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20 mm or any increment therein.

Mechanisms of Action

The therapeutic objectives of the presently disclosed embodiments may be effectuated by one or more of the following mechanisms of action. In a first mechanism of action, the pain of hunger is negated, operating under one or more predefined stimulation parameters. Small diameter nerve fibers carry pain stimuli through a theoretical “gate mechanism” but larger diameter nerve fibers can inhibit the transmission of pain stimuli by the smaller nerves, in effect blocking or closing this theoretical gate. It is believed that by stimulating the large nerve fibers, the gate can be closed to block the pain and thereby block any sensation of hunger. In a second mechanism of action, the production of endorphins, which are natural pain relieving hormones produced by the body, may be upregulated or increased, operating under one or more predefined stimulation parameters, again thereby blocking any sensation of hunger.

In a third mechanism of action, the present embodiments, operating under one or more stimulation parameters, causes a somato-somatic, somato-autonomic and/or a somato-visceral reflex with resulting afferent central as well as efferent visceral effects. In various embodiments, electrical stimulation from the external surface of the patient’s epidermal layer through the dermis of the dermatomes disclosed herein creates a somato-autonomic reflex with sensory nerves that connect specifically to the stomach as an efferent pathway. As a consequence of this

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PCT/ÜS2016/019416 parasympathetic stimulation, the stomach slows down its emptying process and increases the feeling of fullness or satiation, which translates into a reduction in appetite. Similarly, in various embodiments, electrical stimulation from the external surface of the patient’s epidermal layer through the dermis of certain dermatomes, such as the T7 dermatome, also creates a somatoautonomic reflex with sensory nerve endings to dermatome T7 as an afferent pathway and parasympathetic branches of the sensory nerves which stimulate the pancreatic gland as an efferent pathway.

In a fourth mechanism of action, the present application discloses a method of modifying an individual’s perception of food, or otherwise undermining their association of positive feelings with food, and thereby increasing his or her aversion to food intake comprising: providing an electrical dermal patch adapted to adhere to the patient’s epidermal layer, wherein said electrical dermal patch comprises a controller, at least one electrode adapted to be in electrical contact with said patient’s epidermal layer, and a pulse generator in electrical communication with the controller and said at least one electrode, defining a plurality of stimulation parameters, and programming the pulse generator to generate a plurality of electrical pulses using said plurality of stimulation parameters, wherein said plurality of stimulation parameters are defined such that, after applying at least one stimulation to the patient’s epidermal layer, the patient has an increased aversion to food intake. In this regard, the stimulation parameters may be defined such that a) the stimulation is painful, b) the stimulation is coordinated with, and automatically triggered during, the person’s actual food intake times, such times being programmed into the controller or pulse generator either directly or from an external device and automatically triggering a stimulation at the appropriate times, c) the stimulation is coordinated with, and automatically triggered during, times of day other than the person’s actual food intake times, such times being programmed into the controller or pulse generator either directly or from an external device and automatically triggering a stimulation at such times, and d) the stimulation is manually triggered at any given time by the patient, either directly via an interface on the EDP or via the external device, as the patient may require. The benefit of this method is that it achieves, in addition to the physiological effects of appetite modulation, the psychological effect of associating a negative sensation (electrical stimulation) with food intake, thereby undermining the otherwise positive associations the individual has with food and,

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PCT/ÜS2016/019416 therefore, one of the key psychological impetuses for compulsive eating. In this regard, the present invention achieves an aversion to food intake, in addition to a decrease in appetite.

In a fifth mechanism of action, the presently disclosed embodiments selectively cause electrical central nervous stimulation over electrical spinal stimulation. Electrical stimulation in the perceptive range is central (sensory) and in the non-perceptive range is spinal (autonomic). Electrical stimulation above a sensation reaction threshold results in selective central stimulation while electrical stimulation below the sensation reaction threshold results in selective spinal stimulation. Therefore, determining the sensation reaction threshold in a patient allows for the adjustment of electrical stimulation parameters for selective central or spinal stimulation to modulate the patient’s appetite level.

FIG. 27A is a flow chart illustrating the steps involved in one embodiment of a method of determining stimulation reaction thresholds and using an electro-dermal patch (EDP) device to suppress appetite in a patient. At step 2722, the EDP device is positioned on the patient’s body. At step 2724, a central electrical stimulation reaction threshold for the patient is determined. Then, at step 2726, a spinal electrical stimulation reaction threshold for the patient is determined. A microcontroller of the EDP device is then programmed, at step 2728, such that at least one of a pulse width, pulse amplitude, and pulse frequency of delivered electrical stimulation is set above the spinal electrical stimulation reaction threshold but below the central electrical stimulation reaction threshold. At step 2730, the EDP device then generates a plurality of electrical pulses defined by tire pulse width, pulse amplitude, and pulse frequency set at step 2728.

FIG. 27B is a flow chart illustrating the steps involved in another embodiment of a method of determining stimulation reaction thresholds and using an electro-dermal patch (EDP) device to suppress appetite in a patient. At step 2742, the EDP device is positioned on the patient’s body. At step 2744, a maximum tolerable electrical stimulation reaction threshold, which can be measured as a pain sensation, for the patient is determined. Then, at step 2746, a spinal electrical stimulation reaction threshold for the patient is determined. A microcontroller of the EDP device is then programmed, at step 2748, such that at least one of a pulse width, pulse amplitude, and pulse frequency of delivered electrical stimulation is set above the spinal electrical stimulation reaction threshold but below the maximum tolerable electrical stimulation reaction threshold. At step 2750, the EDP then generates a plurality of electrical pulses defined by the pulse width, pulse amplitude, and pulse frequency set at step 2748.

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In a sixth mechanism of action, the electro-dermal patch (EDP) devices of the present specification stimulate specific dermatomes as described above to modulate ghrelin and suppress appetite. The gastric mucosa plays a role in ghrelin-induced gastric contractions. Intrinsic primary afferent neurons (ΙΡΑΝ), which comprise multi-axonal interneurons, may be involved in passing signals from the mucosa to the myenteric plexus. Ghrelin may stimulate and modulate gastric contractions through cholinergic, adrenergic, serotonergic, and/or opioidergic actions and/or via nitric oxide synthase in the myenteric plexus. The stimulatory effects of ghrelin on gastric motility are mediated by the direct stimulation of the intrinsic enteric neural pathway and capsaicin-sensitive afferent neurons. There exists a close interaction between grelin and enteric neurotransmission, involving the stimulation of the excitatory neural system and/or the suppression of the inhibitory neural system via ghrelin receptors, under stimulation of the intrinsic neural pathways. Ghrelin secretion during fasting is induced by adrenergic agents (locally released norepinephrine), released by sympathetic neurons acting directly on Bl receptors on ghrelin secreting cells of the stomach, resulting in fasting-induced elevation in plasma ghrelin levels.

Sympathetic stimulation at certain dermatomes, such as dermatome T6, causes a somatovisceral arc reflex which causes inhibition of the Bl adrenergic (sympathetic) neurons that produce ghrelin. This results in a decrease in ghrelin levels. This decrease in ghrelin causes activity in the enteric nervous system and intrinsic primary afferent neurons contained in the gastric mucosa (necessary as a final step in ghrelin’s action on gastric and antral motility).

Therefore, in various embodiments of the present specification, the EDP devices are believed to suppress appetite via the following mechanism. To begin, an EDP device delivers electrical stimulation to the cutaneous nerves at dermatome T6 (or any of the other dermatomes described in the present specification), activating the somato-visceral reflex described above, hr some embodiments, the EDP device delivers electrical stimulation to the cutaneous nerves at dermatomes T5 - T10. Stimulation of the Bl adrenergic plexus (neurons), which is inhibitory in nature, results in decreased production of fasting ghrelin. This leads to decreased activity in the enteric nervous system and in intrinsic primary afferent neurons (responsible for the final steps necessary for ghrelin action on gastrointestinal motility). The decreased plasma ghrelin levels result in appetite suppression as well as decreased gastric motility and decreased gastric emptying time.

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In a sixth mechanism of action, the electro-dermal patch (EDP) devices of the present specification use electrical stimulation to effect a reduction in antral activity resulting in reduction in gastric motility and slowing of gastric emptying. Somatic stimulation of the T2-T12 and/or C5-T1 dermatomes, using the electro-dermal patch device of the present specification, affects modulation of the gastrointestinal phasic pressure activity resulting in reduction in antral motility and an increase in plasma beta-endorphin levels. Thus, somatic stimulation causes reduced post-prandial antral phasic pressure activity, slowing of gastric emptying and therefore a feeling of satiety over increased periods of time between meals. FIG. 47A is a chart 4700 illustrating mean cumulative changes (in 20 minutes increments) of antral motility indices during sham stimulation sessions 4705, stimulation sessions 4710 targeted to hand dermatomes C8 and/or Tl and stimulation sessions 4715 targeted to thoracic dermatomes T2-T12. Note the effect on antral motility of the hand and abdomen stimulation sessions. FIG. 47B is a chart 4701 illustrating maximum plasma endorphin levels in pg/ml related to sham stimulation sessions 4706, stimulation sessions 4711 targeted to hand dermatomes C5 - C8 and/or Tl and stimulation sessions 4716 targeted to thoracic dermatomes T2-T12. Note the increase in endorphin levels as a result of the hand and abdomen stimulation sessions. In additional mechanisms of action, the electro-dermal patch (EDP) devices of the present specification use electrical stimulation to modulate gut microbiota to improve the ratio of favorable to unfavorable gut bacteria, modulate secretions of a plurality of hormones such as serotonin, glucagon-like peptide 1 (GLP1), and leptin, reduce serum levels of lipopolysaccharide (LPS), improve metabolic inflammation and insulin resistance, modulate resting metabolic rate (RMR) and by improving glucose homeostasis. The specific therapeutic objectives related to each of the above listed hormones and other physiological markers are further discussed below.

Stimulation Patterns/Protocols to Drive Therapy

As discussed earlier, the user’s plurality of health related information, such as the user’s hunger profile, standard eating and meals profile, actual eating and meals profile, energy balance, weight trends, glucose data, stimulation induced nausea, dyspepsia and habituation events - is utilized by the Health Management application to suggest and/or implement a plurality of recommendations comprising stimulation patterns or protocols, medication (such as an amount of insulin intake, for example), dietary and/or activities plans. It should be appreciated that this

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<td> Breakfast</td><td> Skimmed milk 200 cc or 2 natural skimmed yoghourts Bread 50 g or 2 toasts of “biscotti” type bread</td>

<td> Mid-morning</td><td> Fruit (one piece, 100 g of apple, pear, orange, melon or kiwi)</td>

<td> Meal and dinner</td><td> Main course to choose from: Vegetables 200 g: spinach, chard, eggplant, watercress, endive, lettuce, cauliflower, mushroom, leek, asparagus, escarole, cabbage, cucumber, peppers, tomatoes, alternating cooked or in a salad, or 150 g of green beans, beet, carrot, artichoke or Brussels sprouts Vegetable soup Skimmed broth (free consumption) Andalusian gazpacho, provided it is prepare without bread and a small amount of oil, remembering not to exceed the ration of oil for die whole day Pasta, semolina, rice or tapioca soup (15 g dry) Second course to choose from: White fish 120 g Chicken, turkey, rabbit, veal meat 100 g Eggs, one unit Tomatoes and lettuce salad (or any other raw vegetable) 150 g only once a day Dessert, to choose from: Fruit (one piece, 100 g of apple, pear, orange, kiwi, melon or 200 g of watermelon) Bread 25 g</td>

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PCT/ÜS2016/019416 recognizes the need for greater stimulation as indicated by the higher score and titrates therapy accordingly. For example, in one embodiment, if the patient enters a hunger score greater than 3 in the patient diary over a period of four to seven consecutive days within the first week, the algorithm uses the score to incrementally increase the duration of each stimulation session. If after three weeks the patient enters a hunger score greater than 3 in the patient diary for 3 consecutive days, the algorithm uses the score to increase the number of stimulation sessions per day. Conversely, a lower hunger score indicates stimulation needs to be decreased. For example, if the patient enters a hunger score of 1 for three consecutive days within the first week, stimulation sessions are decreased in duration and frequency. In other embodiments, the hunger score scale extends from 1 to 10.

In other embodiments, rather than a scale to determine the presence or absence of hunger, the system presents the patient with a scale configured to record changes in his hunger after stimulation. For example, in an embodiment, a hunger change score scale extends from 1 to 3 wherein 1 is indicative of no change, 2 is indicative of some change, and 3 is indicative of significant change in hunger after stimulation. If a patient reports a 1, no change in hunger after stimulation, stimulation parameters are increased.

For appetite, referring to FIG. 11, the patient can enter an appetite score from 1 to 5, wherein 1 indicates the patient ate substantially less than his diet, 2 indicates the patient ate a little less than his diet, 3 indicates the patient followed his diet, 4 indicates the patient somewhat exceeded his diet, and 5 indicates the patient substantially exceeded his diet. As with the hunger score discussed above, in some embodiments, an appetite score having a higher numerical value indicates appetite suppression is inadequate and the patient requires greater stimulation. The treatment algorithm of the companion device recognizes the need for greater stimulation as indicated by the higher score and titrates therapy accordingly. For example, in one embodiment, if the patient enters an appetite score greater than 3 in the patient diary over a period of four to seven consecutive days within the first week, the algorithm uses the score to incrementally increase the duration of each stimulation session. If after three weeks the patient enters an appetite score greater than 3 in the patient diary for 3 consecutive days, the algorithm uses the score to increase the number of stimulation sessions per day. Conversely, a lower appetite score indicates stimulation needs to be decreased. For example, if the patient enters an appetite score

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100mm VAS line. At the first occasion (pré-stimulation), each patient’s responses or scores to the VAS satiety questionnaire were recorded at intervals of every 60 minutes starting from a first response or score 3706a through 3706e that, in one embodiment, is recorded just prior to a meal (such as breakfast) but without subjecting any of the patients to stimulation therapy. At the second occasion (post-stimulation), each patient’s responses or scores to the VAS satiety questionnaire were again recorded at intervals of every 60 minutes starting from a first response or score 3707a through 3707e recorded just prior to the meal (such as breakfast) but after having treated each of the patients with stimulation therapy prior to, for example 30 minutes before, the meal. In accordance with an embodiment, the responses or scores related to the first occasion are recorded on a first day while those related to the second occasion are recorded on a second day, preferably at the same time of day and under the same eating or fasting conditions as the first day.

As shown in FIG. 37A, the first patient’s satiety responses or scores for the first occasion (that is, pre-stimulation) are recorded on a first day and plotted on a graph, whose x-axis represents time in minutes and y-axis represents VAS satiety responses or scores in millimeters, to generate a pre-stimulation satiety profile 3705a. Thereafter, the first patient is subjected to stimulation therapy, in accordance to embodiments of the present specification, and the satiety responses or scores for the second occasion (that is, post-stimulation) are also plotted on the graph to generate a post-stimulation satiety profile 3708a. Similarly, the second, third, fourth and fifth patients’ responses or scores are recorded to generate the respective pre-stimulation satiety profiles 3705b, 3705c, 3705d, 3705e and the respective post-stimulation satiety profiles 3708b, 3708c, 3708d, 3708e as shown in FIGS. 37B through 37E. As can be observed from FIGS. 37A through 37E, the post-stimulation satiety profiles 3708a, 3708b, 3708c, 3708d, 3708e reflect reduced satiety magnitude relative to the pre-stimulation satiety profiles 3705a, 3705b, 3705c, 3705d, 3705e. In some embodiments, the post-stimulation satiety profile of a patient reflects at least a 5% increase in satiety magnitude relative to the patient’s pre-stimulation satiety profile.

FIG. 37F shows a first bar 3710 representing a median AUC pre-stimulation satiety score derived from AUC values for pre-stimulation satiety profiles of at least one patient, a second bar 3711 representing a median AUC end-of-stimulation satiety score derived from AUC values for end-of-stimulation satiety profiles (that is, the satiety profiles recorded starting immediately after the end of stimulation therapy) of the at least one patient and third bar 3712 representing a median AUC post-stimulation satiety score derived from AUC values for post-stimulation satiety

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PCT/ÜS2016/019416 profiles of the at least one patient. In various embodiments, end-of-stimulation is defined as the end of a period of stimulation lasting in a range from one session to a multitude of sessions over six months. In various embodiments, post-stimulation is defined as a time after the cessation of therapy and ranges from one day after cessation to six months after cessation. As shown in the figure, the median AUC satiety scores 3711, 3712 corresponding to end-of-stimulation and poststimulation scenarios are elevated or improved relative to the median AUC satiety score 3710 corresponding to the pre-stimulation scenario. In other words, the stimulation therapy of the present specification results in hunger suppression or improved satiety. In some embodiments, an area under the curve (AUC) of the post-stimulation satiety profile of a patient reflects at least a 5% increase relative to the patient’s AUC of the pre-stimulation satiety profile.

PCT/ÜS2016/019416 parameters. Although embodiments having three primary drivers and two secondary indicators have been discussed, additional embodiments having greater or fewer primary drivers and/or secondary indicators are possible and the variables presented are not intended to be limiting.

The EDP devices of the present specification can be used to enable a patient to comply with a dietary plan. In some embodiments, the system calculates, for example, via an application or software on the microprocessor of the EDP, the timing of food consumption by the patient, the total calories consumed, and the type of food consumed (i.e. glycemic index, carbohydrate profile, and protein profile). The system then, via an algorithm through said application or software, uses the calculated information to titrate electrical stimulation therapy. For example, if the patient eats outside his normal dietary time, eats too many calories based on his diet, and/or eats foods high in glycemic index or carbohydrate profile, the system recognizes this and increases any one or combination of stimulation amplitude, frequency, number of sessions, session length, or session timing.

Specifically, in various embodiments, the system calculates timing of consumption, total calories consumed, and type of food consumed, as described above, along with other parameters such as exercise and on-going weight loss, and, based on the calculations, performs the following therapy adjustments:

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PCT/ÜS2016/019416 elapsed at step 3218, the patient diary application initiates a modification to the default parameter setting, which may or may not result in immediate stimulation, wherein the modification may include an increment or a decrement to any stimulation or timing variable.

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PCT/ÜS2016/019416 the patient overeats at a specific time and continues to depict such overeating behavior over a predefined period of time, for example, 3 to 5 days, the companion device may change the timing of stimulation to just prior (for example, a half hour or an hour prior) to the overeating meal event or time or may include an additional stimulation session just prior to the overeating meal event. In some embodiments, the energy balance and glycemic load are calculated for every meal of the day, which in turn enables calculation of the meal that contributes the highest percentage of calories (or energy surplus) and glycemic load for the day. This meal, which contributes the highest percentage of calories and glycemic load per day over a predefined period of time, is identified as the overeating meal event.

During the treatment cycle, if the patient stops exercising for a predefined period of time, for example 3 to 5 days, or if the patient has an exercise score of 5 (FIG. 12), indicating the least level of expected exercising and therefore calories expended, and is also at a surplus energy balance for a predefined period of time (for example 3 to 5 days), the companion device ramps up stimulation parameters at step 3420. At step 3422, following a treatment course or cycle, once the patient has lost sufficient weight or achieved a target weight, the companion device modifies stimulation parameters to a maintenance mode wherein the stimulation parameters such as stimulation intensity, duration and number of sessions are all lowered.

Optionally, at step 3424, the companion device provides the patient with the option of sharing his results via social media with designated friends and family. In an alternate embodiment, the companion device first accumulates patient diary data before the EDP device is set into the default operation mode. Referring to FIG. 34, in this alternate embodiment, step 3408 is performed prior to step 3404. The remaining steps proceed in the same order.

Therapeutic Objectives

In various embodiments, the systems and methods of the present specification employ an electro-dermal patch that provides pre-programmed and/or customized stimulation protocols to induce changes in antral and gastric motility to slow passage of food. In various embodiments, a Health Management application software, as described above, provides and/or enables the programming, either pre-programmed or set ‘on demand’ by the patient or medical personnel (in real time), of a plurality of therapeutic goals which are also customizable or adjustable in order to modulate gut hormones, modulate gut microbiota, assess antral and gastric motility, suppress

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PCT/ÜS2016/019416 appetite, achieve dietary compliance, suppress hunger, or elevate fullness, satiation, or satiety. It should be noted herein that any or a plurality of the methods of use or treatment examples provided above may be employed to achieve the therapeutic objectives.

It should also be noted that the percent changes in value listed below are represented by the following formula: [(New Value)-(Old Value)]/(Old Value)]. Thus, where a certain parameter is measured in percentage, the percentage change is reflected by the above formula and not a delta value.

The following are a plurality of non-limiting, exemplary goals:

In some embodiments, after at least one stimulation session or determinable time period after when stimulation terminates, the rate, level or amount of any patient parameter, as discussed throughout this specification is modified relative to Ihe rate, level or amount of that patient parameter before stimulation. In one instance, after at least one stimulation session or determinable time period after when stimulation terminates, the rate, level or amount of that patient parameter is reduced relative to the rate, level or amount of that patient parameter before stimulation. In another instance, after at least one stimulation session or determinable time period after when stimulation terminates, the rate, level or amount of that patient parameter is increased relative to the rate, level or amount of that patient parameter before stimulation.

In some embodiments, after stimulation terminates, or at least one minute from when stimulation terminates, the patient experiences a decrease in appetite or hunger by at least 5%.

In some embodiments, after at least one minute from when stimulation terminates or after at least one stimulation session, the patient experiences a decrease in appetite or hunger such that it is equal to, or less than, 95% of the pre-stimulation appetite or hunger levels.

In some embodiments, after at least one minute from when stimulation is initiated, the patient experiences a perceptible decrease in appetite or hunger.

In some embodiments, after at least one minute from when stimulation is initiated, the patient experiences an increase in satiety, satiation or fullness levels by at least 5%.

In some embodiments, after at least one minute from when stimulation terminates or after at least one stimulation session, the patient experiences an increase in satiety, satiation or fullness levels such that it is equal to, or greater than, 105% of the pre-stimulation satiety, satiation or fullness levels.

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In some embodiments, after at least one stimulation session, a patient’s resting metabolic rate increases by at least 1%, and preferably at least 3%, relative to the patient’s resting metabolic rate before stimulation.

PCT/ÜS2016/019416

In some embodiments, application of electrical stimulation via the EDP embodiments disclosed herein result in a person having increased exercise output, defined as the amount of calories burned in a given time period or steps taken in a given time period. Specifically, when the EDP therapy is applied, the stimulation parameters are selected such that, after at least one stimulation session, exercise output of the patient increases by at least 1% relative to the exercise output of the patient before stimulation. This exercise output may be measured over a single day, week, month or other time period.

Achieving Dietary Compliance

In one embodiment, use of the EDP device, in accordance with the methods described herein, result in patients being able to better comply with a predefined dietary regime, including being better able to restrict daily caloric intake to a predefined amount, being better able to adhere to a diet designed to maximize particular nutritional components, such as vitamins, minerals, and proteins, and decrease undesirable nutritional components, such as carbohydrates, fat, and sugars, and being better able to adhere to a diet designed to have a glycemic index that is equal to or less than a predefined amount. The present specification facilitates adhering to dietary objectives for overweight (body mass index of 25-29.9) or obese (body mass index of 30 or greater) individuals, particularly given that willpower alone or even willpower with exercise is an ineffectual approach to dietary compliance and either weight loss or weight management.

WO 2016/138176

PCT/ÜS2016/019416

WO 2016/138176

PCT/ÜS2016/019416 antenna, fractal antenna, or other such antenna that can efficiently receive the transmitted RF power. An external wireless device 4510 transmits the RF signal 4511 to the EDP device 4500. It should be appreciated that wireless energy, in the form of electromagnetic energy, RF energy, ultrasound energy, or any combination thereof, is transferred from the external wireless device 4510 (such as a smartphone, for example) to the EDP device 4500. An embodiment can use a half-wave rectifier, a full-wave rectifier, or any other passive rectifier circuits known in the art, for the passive rectifier circuit. An embodiment can have one antenna 4505 or an additional second antenna 4506 to account for RF signal polarization. The electrodes 4503, 4504 can be percutaneous and/or skin surface electrodes. An embodiment would contain sufficient electronic intelligence to avoid unintended stimulation from another external wireless device, whether that be another patient controller or some other wireless device; e.g., airport security scanner, etc. Such intelligence can be in the form of reading a specific data packet encoded in the RF transmission by means of modulation, such as amplitude modulation, frequency shift keying modulation, or other such conventional techniques.

An embodiment for an external wireless device 4510 is a battery powered portable device. An embodiment for the external wireless device can be a smartphone or any other commerciallyavailable mobile electronics platform (such as that shown in FIG. 44). An embodiment can include an attachment 4512 to a smartphone or commercially-available mobile electronics platform which includes one or more of the following: an antenna, an RF signal generator circuit, an RF communication circuit, and an additional portable power source (e.g., battery). An embodiment for the external wireless device can be portable, thereby incorporating a portable power source. An embodiment for the external wireless device can be non-portable, thereby not requiring a portable power source and able to rely on the use of AC mains (connection to electrical wall socket). An embodiment includes the ability to encode data in the RF transmission to enable pairing to a desired EDP device only.

FIG. 46 is another non-preferred embodiment similar to that of FIGS. 40 and 45 combined. More specifically, the EDP device 4605 has the electrodes, antenna, and rectifier circuit fully implanted. The target dermatome(s) are stimulated through this small structure that has a plurality of anodes and a plurality of cathodes and is placed in the subcutaneous region 4606 of patient’s body 4607 proximate the target dermatome(s). Wireless energy 4601, in the

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PCT/ÜS2016/019416 form of electromagnetic energy, RF energy, ultrasound energy, or any combination thereof, is transferred from an external wireless device 4600 with embodiments as described in FIG. 45.

Telemedicine

As discussed earlier, the electro-dermal patch device is in data communication with and controlled by the companion device. The companion device is further capable of being in data communication with one or more remote patient care facilities and/or patient care personnel enabling telehealth or e-health and therefore allowing health care professionals to evaluate, diagnose and treat patients in remote locations using telecommunications technology.

In accordance with an aspect of the present specification, the user’s plurality of health related information, such as the user’s hunger profile, standard eating and meals profile, actual eating and meals profile, energy balance, weight trends, glucose data, daily or periodic scores related to hunger, appetite, exercise and well-being, stimulation induced nausea, dyspepsia and habituation events, including stimulation protocols, setting and parameters are recorded, archived and stored by the Health Management application software on the Cloud (for example). In various embodiments, such recorded and archived health related information as well stimulation protocols, settings and parameters of the user are communicated to one or more remote care facilities and/or patient care personnel in real time, on-demand and/or periodically.

This enables the user to communicate his health status, trends, treatment or therapy details as well as therapeutic outcomes to the remote care facility and/or patient care personnel for evaluation, advice, support and further treatment and/or medication options. For example, weight loss programs focused on diets often fail due to weight gain after the termination of the program. However, the Health Management application software, which may be HIPAA compliant, enables continuous weight maintenance by: enabling remote monitoring of the user’s weight, blood glucose, blood pressure, and overall activity level, for example; supporting a plurality of modes of communication such as, but not limited to, video-conferencing, teleconferencing, email, and chat to enable interactive, real-time and/or asynchronous weight maintenance related advice or stimulation regimen for the user. For example, the user’s nutrition specialist, fitness trainer and/or a concierge service associated with the EDP device and Health Management application of the present specification may access, process and analyze the user’s health related information and provide interventions in the form of adjusted or modified

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PCT/ÜS2016/019416 stimulation parameters, settings and protocols; modifications to exercising routines, forms, frequency and period; and/or adjustments to the user’s dietary plan.

Hydrolysis of Adipose Tissues

In accordance with an aspect, stimulation of the sympathetic nerves using the EDP device of the present specification allows for innervation of white adipose tissue to hydrolyze them. Even after losing weight, there are spots or areas that remain with a high amount of adipose tissue (for example hip or upper arm or love handles on the trunk). In some embodiments, these spots or areas are stimulated over long periods of time, for example daily, to hydrolyze the 10 adipose tissue accumulated in these spots or areas.

The above examples are merely illustrative of the many applications of the methods and systems of present specification. Although only a few embodiments of the present invention have been described herein, it should be understood that the present invention might be embodied in many other specific forms without departing from the spirit or scope of the invention. Therefore, 15 the present examples and embodiments are to be considered as illustrative and not restrictive, and the invention may be modified within the scope of the appended claims.

Contents439

53 members in 6 offices

This recordMember, by publication datePriority claim

Priority claims35

Priority claims
Document	Office	Kind	Date
62120067	United States of America	–	2015-02-24
62120082	United States of America	–	2015-02-24
201562120082	United States of America	P	2015-02-24
201562120067	United States of America	P	2015-02-24
62133526	United States of America	–	2015-03-16
62133530	United States of America	–	2015-03-16
201562133526	United States of America	P	2015-03-16
201562133530	United States of America	P	2015-03-16
62141328	United States of America	–	2015-04-01
62141333	United States of America	–	2015-04-01
201562141328	United States of America	P	2015-04-01
201562141333	United States of America	P	2015-04-01
62161353	United States of America	–	2015-05-14
62161362	United States of America	–	2015-05-14
201562161362	United States of America	P	2015-05-14
201562161353	United States of America	P	2015-05-14
62189800	United States of America	–	2015-07-08
62189805	United States of America	–	2015-07-08
201562189800	United States of America	P	2015-07-08
201562189805	United States of America	P	2015-07-08
62237356	United States of America	–	2015-10-05
201562237356	United States of America	P	2015-10-05
62240808	United States of America	–	2015-10-13
201562240808	United States of America	P	2015-10-13
62242944	United States of America	–	2015-10-16
62242957	United States of America	–	2015-10-16
201562242944	United States of America	P	2015-10-16
201562242957	United States of America	P	2015-10-16
62246526	United States of America	–	2015-10-26
201562246526	United States of America	P	2015-10-26
62247113	United States of America	–	2015-10-27
201562247113	United States of America	P	2015-10-27
62248059	United States of America	–	2015-10-29
201562248059	United States of America	P	2015-10-29
2016019416	United States of America	W	2016-02-24

Members53

Family members, oldest first
Document	Office	Kind
CA2977584A1	Canada	A1	2016-09-01
CA3227448A1	Canada	A1	2016-09-01
WO2016138176A1	World Intellectual Property Organization (WIPO)	A1	2016-09-01
US2017021171A1	United States of America	A1	2017-01-26
US2017021172A1	United States of America	A1	2017-01-26
US2017080207A1	United States of America	A1	2017-03-23
WO2017075359A2	World Intellectual Property Organization (WIPO)	A2	2017-05-04
US2017128722A1	United States of America	A1	2017-05-11
WO2017075359A3	World Intellectual Property Organization (WIPO)	A3	2017-07-06
WO2017205047A2	World Intellectual Property Organization (WIPO)	A2	2017-11-30
EP3261712A1	European Patent Office (EPO)	A1	2018-01-03
US2018000347A1	United States of America	A1	2018-01-04
WO2017205047A3	World Intellectual Property Organization (WIPO)	A3	2018-01-04
US2018078754A1	United States of America	A1	2018-03-22
US2018085580A1	United States of America	A1	2018-03-29
US9956393B2	United States of America	B2	2018-05-01
WO2018081423A1	World Intellectual Property Organization (WIPO)	A1	2018-05-03
US2018125689A1	United States of America	A1	2018-05-10
CN108271363A	China	A	2018-07-10
EP3261712A4	European Patent Office (EPO)	A4	2018-10-31
US10118035B2	United States of America	B2	2018-11-06
US10143840B2	United States of America	B2	2018-12-04
US10154922B1	United States of America	B1	2018-12-18
US10335302B2	United States of America	B2	2019-07-02
US10376145B2	United States of America	B2	2019-08-13
EP3532148A1	European Patent Office (EPO)	A1	2019-09-04
US2019328565A1	United States of America	A1	2019-10-31
US10463854B2	United States of America	B2	2019-11-05
US2020155001A1	United States of America	A1	2020-05-21
US2020155847A1	United States of America	A1	2020-05-21
US2020164209A1	United States of America	A1	2020-05-28
EP3532148A4	European Patent Office (EPO)	A4	2020-07-08
US10765863B2	United States of America	B2	2020-09-08
US10864367B2	United States of America	B2	2020-12-15
US2021128906A1	United States of America	A1	2021-05-06
WO2021108203A1	World Intellectual Property Organization (WIPO)	A1	2021-06-03
US11197613B2	United States of America	B2	2021-12-14
US2022062621A1	United States of America	A1	2022-03-03
CA3192384A1	Canada	A1	2022-03-17
WO2022056539A1	World Intellectual Property Organization (WIPO)	A1	2022-03-17
US11331482B2	United States of America	B2	2022-05-17
US11369501B2	United States of America	B2	2022-06-28
CN108271363B	China	B	2022-08-09
CN115227969A	China	A	2022-10-25
KR20220148156A	Republic of Korea	A	2022-11-04
US2022362556A1	United States of America	A1	2022-11-17
EP4211635A1	European Patent Office (EPO)	A1	2023-07-19
US11712562B2	United States of America	B2	2023-08-01
US2023285745A1	United States of America	A1	2023-09-14
CA2977584CThis record	Canada	C	2024-03-05
EP3261712B1	European Patent Office (EPO)	B1	2024-04-03
US11957895B2	United States of America	B2	2024-04-16
EP4211635A4	European Patent Office (EPO)	A4	2024-10-09

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