DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable by Starkebaum(US 9937344 B2) in view of Perez(US 20180085580 A1), and further in view of Thornton(US 20170021174 A1) (all references cited previously).
Regarding claim 1, Starkebaum discloses a system for stimulating an anatomical element of a patient, comprising: an implantable pulse generator configured to generate a current; an electrode device electrically coupled to the implantable pulse generator, the electrode device comprising a plurality of electrodes configured for placement on or around the anatomical element of the patient; a processor; and a memory storing data for processing by the processor, the data, when processed, causes the processor to: transmit instructions to the implantable pulse generator(Controllable pulse generator 80 generates an electrical signal waveform, which may comprise a series of pulses with a controlled pulse amplitude, pulse frequency, and pulse width.(detailed description, paragraph 104). For example, processor 40 may generate a series of electrical stimulation pulses consistent with one or more examples waveforms described herein based upon instructions stored in memory 44, and processor 40 may then store the selection in memory 44(detailed description, paragraph 47).Memory 32 stores instructions for execution by processor 30, including operational commands and programmable parameter settings(detailed description, paragraph 37).The overall charge of the series of pulses 66 of waveform 64 may be approximately zero. The charge of each pulse is dependent on the amplitude and pulse width of each respective pulse of the series of pulses 66(detailed description, 73). The proximal ends of leads 18 and 20 are electrically coupled to the pulse generator of IMD 12 via internal conductors to conduct the stimulation pulses to stomach 22 via electrodes 24, 26(detailed description, paragraph 28)). Starkebaum fails to disclose a first waveform with a neutral current and generate the first waveform with the neutral current to have an incrementally increasing amplitude and apply the generated first waveform with the neutral current with the incrementally increased amplitude to the first anatomical element of the patient via the plurality of electrodes of the electrode device manipulate a circadian cycle of a second anatomical element of the patient which causes to achieve a glycemic response in the patient.
However, Perez teaches “Optionally, each of the electrical stimulation pulses is defined by a charged balanced biphasic waveform and wherein the first set of electrical stimulation pulses and second set of electrical stimulation pulses are separated by a predefined time interval[0118]. Optionally, said plurality of stimulation sessions is modified by increasing at least one of a number, an amplitude, a frequency or a pulse width of the electrical pulses of the plurality of stimulation sessions by at least ten percent[0085]. Accordingly, in one embodiment, a first pulse shape is modified to a second pulse shape in response to a determination that the stimulation comprising the first pulse shape is not sufficiently therapeutically effective. The first pulse shape is modified to the second pulse shape by modifying a slope function of the first pulse shape without modifying the overall pulse amplitude by more than 30%, preferably not more than 20%, and more preferably not more than 10%. In another embodiment, the first pulse shape is modified to the second pulse shape by increasing a rate of increase from a minimum pulse amplitude to a maximum pulse amplitude[1279].”
It would be obvious to one of ordinary skill in the art before the effective filing date to configure the electrical stimulation waveforms of Starkebaum with the electrical stimulation system of Perez. Doing so would clarify that the stimulation parameters are determined based on the patient so the patient gets optimized and personalized therapy.
However, Thornton teaches “The device may utilize circadian or other programming as well, so that activation occurs automatically at normal mealtimes for this patient. This may be in addition to the provision for the manual, periodic between meal, and sensing-triggered activation as described above herein[0087]. In some embodiments, the electrical signal is selected for frequency, pulse width, amplitude and timing to downregulate neural activity as described herein[0095]. The first and/or second therapy programs may be applied at the same time, at different times, or at overlapping times. The first and/or second therapy programs may be delivered at specific times of the day, and or in response to a signal from a sensor[0062]”.
It would be obvious to one of ordinary skill in the art before the effective filing date to configure the electrical stimulation waveforms of Starkebaum with the method for glucose regulation of Thornton. Doing so would clarify circadian manipulation of the patient via stimulation.
Regarding claim 2, Starkebaum in view of Perez and Thornton teaches the system of claim 1, but Starkebaum fails to disclose wherein the first anatomical element comprises a celiac vagal trunk and a hepatic vagal trunk of the patient. However, Thornton teaches “In embodiments, the first target nerve is selected from the group consisting of the anterior vagus nerve, the hepatic branch of the vagus nerve, the celiac branch of the vagus nerve, and the posterior vagus nerve. In embodiments, the second target nerve can include the celiac branch of the vagus nerve[0038]”.
It would be obvious to one of ordinary skill in the art before the effective filing date to configure the electrical stimulation waveforms of Starkebaum with the method for glucose regulation of Thornton. Doing so would clarify the branches of the vagus nerve that are stimulated in the system since Starkebaum mentions vagal stimulation but fails to detail specifics.
Regarding claim 3, Starkebaum in view of Perez and Thornton teaches the system of claim 2, wherein the first waveform comprises a frequency between 0.1 and 20 hertz (Hz)(Starkebaum - In another aspect, the disclosure relates to a method comprising delivering a series of pulses with alternating pulse polarities to a patient, wherein the series of pulses includes at least a first pulse of a first polarity, a second pulse of a second polarity, and a third pulse of the first polarity, wherein the first, second and third pulses are delivered in direct succession, in that order, wherein the first and second pulses are separated by a first time delay and the second and third pulses are separated by a second time delay, and wherein the series of pulses are delivered at frequency between approximately 0.05 Hz and 40 Hz(summary, paragraph 6)).
Regarding claim 4, Starkebaum in view of Perez and Thornton teaches the system of claim 3, wherein the first waveform comprises a biphasic pulse(In some examples, such a waveform may be referred to as a “asymmetric biphasic rectangular pulse waveform,” or “asymmetric biphasic pulses waveform,” or “asymmetric biphasic waveform(detailed description, paragraph 7)).
Regarding claim 5, Starkebaum in view of Perez and Thornton teaches the system of claim 4, wherein the first waveform comprises a square wave shape, a trapezoidal wave shape, a sinusoidal wave shape, or another wave shape that is charge balanced(Starkebaum - As will be described in greater detail below, in FIG. 7, a first rectangular stimulation pulse followed by a second, rectangular pulse of opposite polarity(detailed description, paragraph 7)(Fig. 7)).
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Regarding claim 6, Starkebaum in view of Perez and Thornton teaches the system of claim 3, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: transmit instructions to the implantable pulse generator to incrementally increase the frequency, the amplitude, or both of the first waveform when applying the neutral current(For example, processor 40 may generate a series of electrical stimulation pulses consistent with one or more examples waveforms described herein based upon instructions stored in memory 44, and processor 40 may then store the selection in memory 44(detailed description, paragraph 47). Memory 32 stores instructions for execution by processor 30, including operational commands and programmable parameter settings(detailed description, paragraph 37). For example, if the frequency of the delivery of coupled pulse pairs increases, then time intervals T(0), T(1) and T(3) decrease(detailed description, paragraph 64)).
Regarding claim 7, Starkebaum in view of Perez and Thornton teaches the system of claim 6, wherein the frequency, the amplitude, or both of the first waveform are incrementally increased over time to generate a desired shape for the first waveform(Stimulation generator 79 is only one example of a stimulation generator that may be used to generate and deliver stimulation pulses to a patient in a manner consistent with one or more waveforms described in this disclosure. Other example stimulation pulse generators capable of generating and delivering pulses with the desired morphology are contemplated. In other examples, a current regulator may be controlled to operate as a regulated current source or sink and to deliver current pulses with desired polarity, frequency and pulse width to provide any of the waveforms described in this disclosure.(detailed description, paragraph 115). Such pulse “droop” is may be present in some implantable pulse generators, and can be compensated for by increasing pulse amplitude to the point where the trailing edge amplitude equals that of the constant amplitude rectangular pulse being emulated(detailed description, paragraph 102)).
Regarding claim 8, Starkbaum in view of Perez teaches the system of claim 1, wherein the data stored in the memory that, when processed causes the processor to transmit instructions to the implantable pulse generator to apply the neutral current using the first waveform further causes the system to: transmit instructions to the implantable pulse generator to apply a pattern of stimulation pulses to the first anatomical element to simulate a physiological neuron spiking behavior at the first anatomical element, wherein the first waveform comprises the pattern of stimulation pulses(During both the active stimulation and recovery periods, the volume-increase effectiveness advantage of Waveform 1 stimulation over either Waveform 2 or Waveform 3 stimulation was statistically significant (p<0.0001)(detailed description, 121). The GES-induced gastric distension reflected in increased barostat balloon volume has been found to activate neurons in brain nuclei linked to satiation and is one likely mechanism by which GES reduces food intake(detailed description, paragraph 122)(Fig. 12)).
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Regarding claim 9, Starkebaum in view of Perez and Thornton the system of claim 8, but Starkebaum fails to specify wherein the first waveform comprises a standard shape that is determined based at least in part on a plurality of patient studies, common physiological patterns, or a combination thereof.
However, Perez teaches “It should be appreciated that in various embodiments, the user's plurality of health related information is utilized by the Health Management application to suggest and/or implement a plurality of recommendations comprising stimulation patterns or protocols[0929]”.
It would be obvious to one of ordinary skill in the art before the effective filing date to configure the electrical stimulation waveforms of Starkebaum with the electrical stimulation system of Perez. Doing so would clarify that the stimulation parameters are determined based on the patient so the patient gets optimized and personalized therapy.
Regarding claim 10, Starkebaum in view of Perez teaches the system of claim 8, but fails to specify wherein the first waveform comprises a shape that is determined based at least in part on observing signaling on the first anatomical element at different stages of a metabolic cycle of the patient.
However, Perez teaches “A first therapy phase is a period of time during which the user is delivered pre-programmed, customized and/or on-demand stimulation sessions. The first therapy phase is characterized by the fact that the user has a first (baseline) metabolic or health state at the beginning of the first therapy phase and a second metabolic or health state at the end of the first therapy phase[1287]”.
It would be obvious to one of ordinary skill in the art before the effective filing date to configure the electrical stimulation waveforms of Starkebaum with the electrical stimulation system of Perez. Doing so would clarify that the stimulation parameters are determined based on the patient so the patient gets optimized and personalized therapy.
Regarding claim 11, Starkebaum in view of Perez and Thornton teaches the system of claim 8, wherein the pattern of stimulation pulses is regular or non- regular(In waveform 60, the coupled pairs of pulses (pulses 62a and 62e, pulses 62b and 62f, and so forth) are delivered at a set frequency, which is consistent with time interval T(0). As described above, the frequency that the coupled pairs of pulses are delivered does not change the timing that between each pulse in a coupled pair(detailed description, paragraph 64)(Fig. 5)).
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Regarding claim 12, Starkebaum in view of Perez and Thornton teaches the system of claim 1, but Starkebaum fails to disclose wherein the second anatomical element comprises a liver of the patient, and wherein manipulating the circadian cycle of the liver downregulates a first nervous system tone associated with the first anatomical element.
However, Thornton teaches “In some cases, signals are applied at specific times. For example, a downregulating signal may be applied before and during meal, followed by a stimulatory signal about 30 to 90 minutes after eating. In another example, a downregulating signal may be applied to the vagus nerve or the hepatic branch of the vagus nerve early in the morning when hepatic glucose is increasing[0125]. The neural regulation signals can influence the amount of glucose produced by the liver, the amount of glucose absorbed from food, and the amount of GIP, GLP-1 and/or ghrelin secreted. The neural regulation provides for a decrease in the amount of insulin required by the subject[0122]. In embodiments, the first target nerve is selected from the group consisting of the anterior vagus nerve, the hepatic branch of the vagus nerve, the celiac branch of the vagus nerve, and the posterior vagus nerve. In some embodiments, the first target organ can include the stomach, esophagus, and liver[0038]”.
It would be obvious to one of ordinary skill in the art before the effective filing date to configure the electrical stimulation waveforms of Starkebaum with the downregulation signaling of Thornton. Doing so would the signals sent out through the body and how they affect multiple elements or systems in the body.
Allowable Subject Matter
Claim 13 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Response to Arguments
Applicant's arguments filed 12/17/2025 have been fully considered but they are not persuasive. Applicant argues that the combination for Starkebaum, Perez, and Thornton fails to disclose “applying the generated first waveform with the neutral current and with the incrementally increased amplitude to the first anatomical element of the patient via the plurality of electrodes of the electrode device to manipulate a circadian cycle of a second anatomical element of the patient which causes a glycemic response in the patient". However, Thornton teaches “In some embodiments, a signal amplitude of 0.5 to 8 mA is adequate for blocking. Other amplitudes may suffice. Other signal attributes can be varied to reduce the likelihood of accommodation by the nerve or an organ. These include altering the power, waveform or pulse width[0139]. The device may utilize circadian or other programming as well, so that activation occurs automatically at normal mealtimes for this patient. This may be in addition to the provision for the manual, periodic between meal, and sensing-triggered activation as described above herein[0087]. In some embodiments, the electrical signal is selected for frequency, pulse width, amplitude and timing to downregulate neural activity as described herein[0095]. The first and/or second therapy programs may be applied at the same time, at different times, or at overlapping times. The first and/or second therapy programs may be delivered at specific times of the day, and or in response to a signal from a sensor[0062]”. Thornton discusses the ability to alter the amplitude of the nerve signal based on the system needs. It also discloses a relationship between a nerve stimulated and how it affects the glycemic response in an organ. The circadian cycle mentioned in the application is representative of the day of day when stimulation occurs to maximize the effect on glycemic response. Thornton explicitly states manipulating the system based on time and selecting specific times of day for stimulation. Therefore, Thornton in combination with Starkebaum and Perez teaches the disclosed material of claim 1, and the proceeding dependent claims 2-12. It is noted that the amendments to claim 13 overcome the prior art rejections.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA CATHERINE ANTHONY whose telephone number is (703)756-4514. The examiner can normally be reached 7:30 am - 4:30 pm, EST, M-F.
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/MARIA CATHERINE ANTHONY/Examiner, Art Unit 3796
/CARL H LAYNO/Supervisory Patent Examiner, Art Unit 3796