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 Objections
Claims 15 and 18-19 are objected to because of the following informalities:
In claim 15, line 2, “one or more of” should read “one or more of:”
In claim 18, line 2, “(TMS-fNIRS), system” should read “(TMS-fNIRS) system,”
In claim 19, line 3, “one or more of” should read “one or more of:”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 9 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 9 recites the limitation “one or more of moderator or mediators” in line 2. In light of the specification, it is unclear what a moderator or mediator embodies in terms of structure and/or function.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 6, and 8-9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tan et al. (CN 107497051), citing to attached translation.
Regarding claim 1, Tan et al. teaches a method (page 7, para. 7, “the working method of the system is as follows:”) comprising:
measuring, via a functional Near-Infrared Spectroscopy (fNIRS) device, a first set of measurements of a treatment region of a patient to be treated (page 8, para. 4, “starting the TMS and fNIRS device, after the subject quiet relaxation, near infrared signal measured before the stimulation, and the measuring time is 15 s to obtain the oxygenated hemoglobin and deoxygenated hemoglobin signal for its amplitude squaring and summation, as the initial energy of the fNIRS signal”);
performing, via a transcranial magnetic stimulation (TMS) device, TMS treatment to the treatment region for therapeutic effect (page 8, para. 4, “then starting TMS stimulation”; page 7, para. 7, “stimulation coil driven by TMS stimulation system, for magnetic stimulation to the cortex of the brain.”);
measuring, via the fNIRS device, a second set of measurements of the treatment region (page 8, para. 4, “after waiting for 15 s, and then measuring the time 15 s of near infrared signal, repeating until the stimulation is ended. hypothetical fNIRS measurement intensity of the stimulation is the period of time x, after calculating each 15 s period of hemoglobin oxygenation and percentage PerOxy and PerDeoxy the energy of the initial energy of deoxygenated hemoglobin, Per=max (PerOxy, PerDeoxy), Per PerOxy and PerDeoxy maximum value”);
determining, by a processor (page 7, para. 8, “the analysis control device comprises…”), an applied dosing of the TMS treatment based on at least one of the first set of measurements or the second set of measurements (page 7, para. 7, “the fNIRS signal collecting module obtains the continuous time length of 30 s near infrared signal by the analyzing control device, analyzing the signal energy and the signal energy percentage after initial resting state of 15 s period, thereby giving a set of stimulation parameters, stimulation coil driven by TMS stimulation system, for magnetic stimulation to the cortex of the brain”); and
outputting control feedback to the TMS device or visualization to a display to adjust one or more parameters or localization of the TMS treatment based on the applied dosing (page 7, para. 7, “the display and control module can see the current stimulation parameters, such as manual/automatic mode selection, resting the motion threshold, current stimulation intensity, stimulation frequency and stimulation time, and can change parameter by LCD touch screen key module”).
Regarding claim 6, Tan et al. teaches the method according to claim 1 as stated above wherein the adjustment includes a frequency of the TMS treatment (page 8, para. 1, TMS stimulation system comprising…a single chip control of the frequency modulation”; page 8, para. 2, “the stimulus intensity and the stimulus frequency can be adjusted”).
Regarding claim 8, Tan et al. teaches the method according to claim 1 as stated above wherein the control feedback to the TMS device or visualization to the display is used to monitor an effectiveness of treatment changes based on the TMS treatment
(page 6, para. 8, “the display and control module, which can be a small liquid crystal screen displays the oxygenated hemoglobin and deoxygenated hemoglobin in real time after change”, essentially, the obtained oxygenated and deoxygenated hemoglobin signals dictate whether or not the stimulation parameters need to be adjusted to ensure the treatment is effective; page 8, paras. 4-6, para. 4 begins with “step 1, making the subject wearing the good experimental device…”).
Regarding claim 9, as best understood in light of the rejection under 35 U.S.C. 112(b) above, Tan et al. teaches the method according to claim 1 as stated above wherein the effectiveness of treatment region changes includes monitoring changes to one or more of moderator or mediators
(page 8, para. 4, “near infrared signal measured before the stimulation, and the measuring time is 15 s to obtain the oxygenated hemoglobin and deoxygenated hemoglobin signal for its amplitude squaring and summation, as the initial energy of the fNIRS signal, then the signal will be compared with the signal. then starting TMS stimulation, after waiting for 15 s, and then measuring the time 15 s of near infrared signal, repeating until the stimulation is ended. hypothetical fNIRS measurement intensity of the stimulation is the period of time x, after calculating each 15 s period of hemoglobin oxygenation and percentage PerOxy and PerDeoxy the energy of the initial energy of deoxygenated hemoglobin, Per=max (PerOxy, PerDeoxy), Per PerOxy and PerDeoxy maximum value”).
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.
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tan et al., in view of Riehl et al. (US 2017/0232267).
Regarding claim 2, Tan et al. teaches the method according to claim 1 as stated above. Tan et al. fails to teach wherein the adjustment includes a coil to treatment region distance adjustment.
Riehl et al. teaches an analogous method for controlling TMS devices wherein the adjustment includes a coil to treatment region distance adjustment (Fig. 1A, articulating arm 12 and TMS coil assembly 20; para. 0050, where the articulating arm 12 allows the TMS coil assembly 20 to be adjusted relative to the patient’s head; para. 0052, where the display 40 may guide an operator to reposition the TMS coil assembly 20 to improve scalp contact).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the method of Tan et al. with the TMS device adjustment assembly of Riehl et al. The ability to adjust the TMS device relative to a subject’s head ensures a proper magnetic field intensity is applied to the patient (Riehl et al., para. 0004).
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tan et al., in view of Etkin et al. (WO 2017189757).
Regarding claim 7, Tan et al. teaches the method according to claim 1 as stated above. Tan et al. fails to teach wherein the adjustment includes a duration of the TMS treatment.
Etkin et al. teaches an analogous method for diagnosing and treating depression with TMS wherein the adjustment includes a duration of the TMS treatment (paras. 0046, and 0051).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the method of Tan et al. with the TMS treatment duration adjustment of Etkin et al. The treatment duration may need to be increased or decreased relative to the original planned treatment protocol in response to a patient’s evoked brain changes. Correspondingly, the ability to adjust the treatment duration and/or parameters establishes a tolerable and effective stimulation for the patient (Etkin et al., paras. 0070 and 0073, and 0083).
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tan et al., in view of Jiang et al. ("Neuroimaging of depression with diffuse optical tomography during repetitive transcranial magnetic stimulation"), hereinafter "Jiang et al."
Regarding claim 11, Tan et al. teaches the method according to claim 1 as stated above. Tan et al. fails to teach wherein the TMS device is configured to generate at least one of: a 12-block sequence of 1 Hz stimulation with 4 sec on and off 26 sec, a 12-block sequence of 10 Hz stimulation with 4 sec on and off 26 sec; or a 48-jittered single pulses stimulation sequence.
Jiang et al. teaches an analogous method for TMS treatment wherein the TMS device is configured to generate at least one of: a 12-block sequence of 1 Hz stimulation with 4 sec on and off 26 sec, a 12-block sequence of 10 Hz stimulation with 4 sec on and off 26 sec (page 5, Figure 2, “Ten hertz stimulation was performed for 4 s followed by 26 s of rest for a total of 12 epochs”); or a 48-jittered single pulses stimulation sequence.
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the method of Tan et al. with the TMS device configured to generate a 12-block sequence of 10 Hz stimulation with 4 seconds on and off 26 seconds of Jiang et al. Implementing a ten hertz stimulation with four second duration per session, constitutes a standard treatment protocol for transcranial magnetic stimulation (TMS) (Jiang et al., page 2, para. 6, “All rTMS treatments were performed with a Neurostar TMS Therapy System (Neuronet ics, Inc., Malvern, PA, USA). Stimulation protocol was followed per the product documentation…”; page 7, para. 2, “10 Hz stimulation has been shown to increase [HbO], which was associated with continued therapeutic effects of TMS”).
Claim(s) 3-5, 10, 12-15, and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tan et al., in view of Kozel et al. ("Using simultaneous repetitive Transcranial Magnetic Stimulation/functional Near Infrared Spectroscopy (rTMS/fNIRS) to measure brain activation and connectivity"), hereinafter "Kozel et al."
Regarding claim 3, Tan et al. teaches the method according to claim 1 as stated above. Tan et al. fails to teach wherein the adjustment includes a gyrus orientation adjustment.
Kozel et al. teaches an analogous fNIRS-TMS system and method wherein the adjustment includes a gyrus orientation adjustment (page 9, para. 3, “subjects were first stimulated over the motor cortex and then the prefrontal cortex”).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the method of Tan et al. with the gyrus orientation adjustment of Kozel et al. Stimulating the prefrontal cortex via transcranial magnetic stimulation is a method frequency employed to treat depression; additionally, by successively stimulating the motor cortex and ipsilateral and contralateral prefrontal cortex where different gyri occupy, bilateral changes in cortical activation and functional brain changes may be induced (Kozel et al., page 2, para. 2, “daily prefrontal rTMS has been found to have antidepressant properties when treating patients with depression “; page 3, para. 5, “produce bilateral changes in cortical activation that would be measurable by fNIRS. Further, we hypothesized that functional brain changes induced by TMS over the motor cortex and the prefrontal cortex”).
Regarding claim 4, Tan et al. teaches the method according to claim 1 as stated above. Tan et al. fails to teach wherein the treatment region is the prefrontal cortex and the adjustment includes a cortical excitability output to a motor cortex and dorsolateral prefrontal cortex.
Kozel et al. teaches an analogous fNIRS-TMS system and method wherein the treatment region is the prefrontal cortex and the adjustment includes a cortical excitability output to a motor cortex and dorsolateral prefrontal cortex (page 5, Visit-2, “simultaneous TMS/fNIRS over the motor cortex and the prefrontal cortex were performed as in Visit 1”; page 7, paragraphs with headings titled: Simultaneous rTMS/fNIRS of Motor Cortex, Simultaneous rTMS/fNIRS of Prefrontal Cortex, and Comparing Prefrontal and Motor Cortices of Simultaneous rTMS/fNIRS).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the method of Tan et al. with the treatment region and cortical excitability output to the motor cortex and dorsolateral prefrontal cortex of Kozel et al. Stimulating the prefrontal cortex via transcranial magnetic stimulation is a method frequency employed to treat depression; additionally, by successively stimulating the motor cortex and ipsilateral and contralateral prefrontal cortex, bilateral changes in cortical activation and functional brain changes may be induced (Kozel et al., page 2, para. 2, “daily prefrontal rTMS has been found to have antidepressant properties when treating patients with depression “; page 3, para. 5, “produce bilateral changes in cortical activation that would be measurable by fNIRS. Further, we hypothesized that functional brain changes induced by TMS over the motor cortex and the prefrontal cortex”).
Regarding claim 5, Tan et al. teaches the method according to claim 1 as stated above. Tan et al. fails to teach wherein the adjustment includes a location of the TMS treatment.
Kozel et al. teaches an analogous fNIRS-TMS system and method wherein the adjustment includes a location of the TMS treatment (Figure 1, where the TMS coil’s location was adjusted relative to the motor cortex and prefrontal cortex; page 5, para. 1, “The fNIRS probes were positioned over the prefrontal cortex (see Figure 1) – defined as 5 cm anterior to the motor cortex position in a para-sagittal line…the coil was moved 5 cm anteriorly in a para-sagittal line. The fNIRS recording and TMS stimulation were exactly the same as for the motor cortex stimulation”).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the method of Tan et al. with the treatment location adjustment of Kozel et al. Adjusting the location of the TMS treatment in order to stimulation the motor cortex and prefrontal cortex may be beneficial for treating patients with depression. While the effects of motor cortex stimulation are easy to observe and quantify, i.e., muscle response, the effects of TMS in areas of the brain, such as the prefrontal cortex, are difficult to observe. As a result, researchers rely on measured hemodynamic changes to evaluate brain responses in the prefrontal cortex. Therefore, by adjusting the location of the TMS coil to first stimulate the motor cortex and then the prefrontal cortex, the measured hemodynamic changes may provide a means to monitor the neuronal changes from TMS, and provide an integrated approach for depression treatment (Kozel et al., page 5, fNIRS Statistical Analysis; page 2, para. 3, “The majority of rTMS (and TMS) studies of brain function and treatment effects have occurred with stimulation of the motor cortex…”; page 3, para. 3, “Functional NIRS offers the potential of measuring immediate brain effects…”).
Regarding claim 10, Tan et al. teaches the method according to claim 1 as stated above. Tan et al. fails to teach wherein the control feedback to the TMS device or visualization to the display is used to determine a stopping criteria for the TMS treatment.
Kozel et al. teaches an analogous fNIRS-TMS system and method wherein the control feedback to the TMS device or visualization to the display is used to determine a stopping criteria for the TMS treatment (page 4, para. 6, “one minute prior to stimulation, during the 15 stimulation/rest epochs (90 seconds per epoch), and during a one-minute poststimulation period resulting in a total recording time of 24 minutes and 30 seconds” wherein the treatment duration, i.e., twenty two and half minutes for the motor cortex stimulation interval, is the stopping criteria).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the method of Tan et al. with the stopping criteria of Kozel et al. Implementing a specific treatment duration that is consistent across various patients ensures the comparability of obtained oxygenated and deoxygenated hemoglobin measurements within a target population (Kozel et al., page 6, para. 5, “a resting motor threshold (RMT) was obtained for nine…; the entirety of page 7).
Regarding claim 12, Tan et al. teaches the method according to claim 1 as stated above.
Tan et al. further teaches wherein the fNIRS device includes a light source and a light detector, at least one of each forming a pair (Fig. 1, near infrared collecting probe 2; page 6, para. 6, “near infrared signal collecting system through the emitting end emits near infrared light, whose wavelength is 850 nm and 760 nm can detect oxygenated hemoglobin and deoxygenated hemoglobin, respectively, can have the same frequency characteristic of the photoelectric receiving diode or photocell as probe”), wherein each pair is configured to be placed a predetermined distance apart from one another (Fig. 4; page 5, para. 9, “the transmitting probe and receiving probe interval is not greater than 6 cm”). However, Tan et al. fails to teach a plurality of lights sources and light detectors.
Kozel et al. teaches an analogous fNIRS-TMS system and method wherein the fNIRS device includes a plurality of light sources and a plurality of light detectors, at least one of each forming a pair, wherein each pair is configured to be placed a predetermined distance apart from one another (page 13, Figure 1. Location of the rTMS coil and fNIRS Sources and Detectors, “The fNIRS probe comprised of 28 source-detector pairs”; as shown in Fig. 1, the source and detectors are spaced equal distance apart and 5 cm anterior to the motor cortex position).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Tan et al. with the plurality of light sources and light detectors of Kozel et al. A plurality of light sources and light detectors provides a variable number of channels (source-detector pairs) which may be manipulated to maximize the uniformity of the acquired fNIRS signals. Furthermore, the multitude of channels may provide an operating system the ability to allocate responsive channels and exclude inconsistent and nonresponsive channels from a pooled analysis (Kozel et al., page 5, the entirety of paragraph 3 titled fNIRS Statistical Analysis).
Regarding claim 13, Tan et al. teaches the method according to claim 1 as stated above.
Tan et al. further teaches wherein the control feedback to the TMS device or visualization to the display is to provide sufficient cortical excitability for neurological treatment (page 1, para. 6, “technical field of nerve disease treatment and brain function research”; page 6, para. 4, “analyzing control device automatically sends stimulation parameter to a transcranial magnetic stimulation system”; page 7, para. 7, “stimulation coil driven by TMS stimulation system, for magnetic stimulation to the cortex of the brain”). Tan et al. fails to teach wherein the TMS treatment is for treatment of depression, and the treatment region is the prefrontal cortex.
Kozel et al. teaches an analogous fNIRS-TMS system and method wherein the TMS treatment is for treatment of depression (page 8, para. 1, “relieve the depressive symptoms”; page 2, para. 2, “daily prefrontal rTMS has been found to have antidepressant properties when treating patients with depression”), the treatment region is the prefrontal cortex (page 5, para. 1, “The fNIRS probes were positioned over the prefrontal cortex (see Figure 1) – defined as 5 cm anterior to the motor cortex position in a para-sagittal line…the coil was moved 5 cm anteriorly in a para-sagittal line. The fNIRS recording and TMS stimulation were exactly the same as for the motor cortex stimulation”).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Tan et al. with the TMS treatment for treatment of depression wherein the treatment region is the prefrontal cortex of Kozel et al. Transcranial magnetic stimulation is an non-invasive therapy proven effective in treating a multitude of neuropsychiatric disorders and diseases; therefore, it would be beneficial to include a treatment region to the prefrontal cortex, where TMS has demonstrated antidepressive properties (Kozel et al., page 2, para. 1, “Transcranial magnetic stimulation (TMS) is a technology that is being used to investigate normal brain function and various neuropsychiatric disorders…”; page 2, para. 2, “rTMS is being investigated as a possible treatment for various brain disorders. As an example, daily prefrontal rTMS has been found to have antidepressant properties when treating patients with depression…”).
Regarding claim 14, Tan et al. teaches a system (Abstract) comprising:
a functional Near-Infrared Spectroscopy (fNIRS) device (page 3, para. 8, “the fNIRS signal collecting system comprises a fNIRS signal collecting module, the storage module, and the communication module”; page 3, para. 10, “Furthermore, the fNIRS signal collecting module comprises an emitting probe and a receiving probe”);
a transcranial magnetic stimulation (TMS) device (Fig. 1, TMS coil 1; page 3, para. 9, “TMS stimulation system comprises a communication module, a power amplifying circuit, a storage module, the single chip control of the frequency modulation amplitude modulation of the magnetic stimulation system”); and
an integrated component having a processor and a memory having instructions stored thereon, wherein execution of the instructions by the processor causes the processor to (page 4, para. 1, “the analysis control device comprises a visible touch liquid crystal display screen, a single chip, a storage module, a power supply circuit”; page 8, para. 3, “the working method of the analyzing control device, comprising:”):
receive a second set of fNIRS measurements of the treatment region (page 8, para. 4, “then starting TMS stimulation, after waiting for 15 s, and then measuring the time 15 s of near infrared signal, repeating until the stimulation is ended”);
determine an applied dosing of the TMS treatment based on one or more of the first set of fNIRS or the second set of fNIRS (page 8, paras. 4-5, “hypothetical fNIRS measurement intensity of the stimulation is the period of time x, after calculating each 15 s period of hemoglobin oxygenation and percentage PerOxy and PerDeoxy the energy of the initial energy of deoxygenated hemoglobin, Per=max (PerOxy, PerDeoxy), Per PerOxy and PerDeoxy maximum value; step 2, according to stimulation mode of the Per value after determining”); and
provide control feedback to the TMS device or visualization to a display to adjust one or more parameters or localization of the TMS treatment based on the applied dosing (page 7, para. 7, “the display and control module can see the current stimulation parameters, such as manual/automatic mode selection, resting the motion threshold, current stimulation intensity, stimulation frequency and stimulation time, and can change parameter by LCD touch screen key module, so as to fNIRS signal through real time control the TMS stimulation”).
Tan et al. fails to teach wherein execution of the instructions by the processor causes the processor to: receive a first set of fNIRS measurements of a treatment region in response to a TMS treatment applied by the TMS device to the treatment region of a patient.
Kozel et al. teaches an analogous fNIRS-TMS system and method wherein a first set of fNIRS measurements of a treatment region are received in response to a TMS treatment applied by the TMS device to the treatment region of a patient (see Annotated Figure 2; page 4, para. 6, “fNIRS data was acquired one minute prior to stimulation, during the 15 stimulation/rest epochs (90 seconds per epoch), and during a one-minute poststimulation period resulting in a total recording time of 24 minutes and 30 seconds”).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the system of Tan et al. with the first set of fNIRS measurements of a treatment region in response to a TMS treatment applied by the TMS device of Kozel et al. fNIRS data acquired in response to a TMS treatment may be employed to conduct a comparative analysis between the brain’s hemodynamic changes associated with TMS of the motor cortex and the prefrontal cortex. Furthermore, fNIRS measurements collected during stimulation may provide insights into the effectiveness of the stimulation parameters and the localization of TMS stimulation (Kozel et al., page 4, para. 6, “After the fNIRS recording was complete, the location of the TMS stimulation relative to the fNIRS system was determined”; page 7, para. 3, “the conditions studied (healthy participants stimulated for 10 secs with 1 Hz rTMS), the brain changes associated with motor cortex stimulation and prefrontal cortex stimulation”; page 7, para. 6, “Gaining a better understanding of how different treatment parameters interact to produce clinical outcome is critical to optimizing the effectiveness of these new treatments”).
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Annotated Figure 2
Regarding claim 15, Tan et al., in view of Kozel et al., teaches the system according to claim 14 as stated above wherein the instruction further causes the processor to provide control feedback to the TMS device (Tan et al., page 5, para. 12, “said analyzing control device connected with the TMS stimulation system and fNIRS signal acquisition system”) or visualization to the display to adjust one or more of: a coil to treatment region distance, a gyrus orientation, an excitability output, a location of the TMS treatment, a frequency of the TMS treatment (Tan et al., Fig. 3; page 8, para. 3, “the working method of the analyzing control device, comprising:” and paras. 5-6, “changing the stimulation intensity [via an adjusting formula] …the same treatment/[formula] [applies] for the stimulation frequency”) a duration of the TMS treatment, an effectiveness of treatment region changes based on the TMS treatment, or a stopping criteria for the TMS treatment.
Regarding claim 17, Tan et al., in view of Kozel et al., teaches the system according to claim 14 as stated above.
Tan et al. further teaches wherein the fNIRS device includes a light source and a light detector, at least one of each forming a pair (Fig. 1, near infrared collecting probe 2; page 6, para. 6, “near infrared signal collecting system through the emitting end emits near infrared light, whose wavelength is 850 nm and 760 nm can detect oxygenated hemoglobin and deoxygenated hemoglobin, respectively, can have the same frequency characteristic of the photoelectric receiving diode or photocell as probe”), wherein each pair is configured to be placed a predetermined distance apart from one another (Fig. 4; page 5, para. 9, “the transmitting probe and receiving probe interval is not greater than 6 cm”). Tan et al. fails to teach a plurality of lights sources and light detectors.
Kozel et al. teaches an analogous fNIRS-TMS system and method wherein the fNIRS device includes a plurality of light sources and a plurality of light detectors, at least one of each forming a pair, wherein each pair is configured to be placed a predetermined distance apart from one another (page 13, Figure 1. Location of the rTMS coil and fNIRS Sources and Detectors, “The fNIRS probe comprised of 28 source-detector pairs”; as shown in Fig. 1, the source and detectors are spaced equal distance apart and 5 cm anterior to the motor cortex position).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the system of Tan et al. with the plurality of light sources and light detectors of Kozel et al. A plurality of light sources and light detectors provides a variable number of channels (source-detector pairs) which may be manipulated to maximize the uniformity of the acquired fNIRS signals. Furthermore, the multitude of channels may provide an operating system the ability to allocate responsive channels and exclude inconsistent and nonresponsive channels from a pooled analysis (Kozel et al., page 5, the entirety of paragraph 3 titled fNIRS Statistical Analysis).
Regarding claim 18, Tan et al. teaches a non-transitory computer-readable medium for a transcranial magnetic stimulation (TMS) functional Near-Infrared Spectroscopy (fNIRS) (TMS-fNIRS) system, the non-transitory computer-readable medium having instructions stored thereon, wherein execution of the instructions by one or more processors causes the one or more processors to (page 4, para. 1, “the analysis control device comprises a visible touch liquid crystal display screen, a single chip, a storage module, a power supply circuit”; page 5, para. 12, “analyzing control device connected with the TMS stimulation system and fNIRS signal acquisition system”):
receive a second set of fNIRS measurements from the fNIRS device of the treatment region (page 8, para. 4, “then starting TMS stimulation, after waiting for 15 s, and then measuring the time 15 s of near infrared signal, repeating until the stimulation is ended”);
determine an applied dosing of the TMS treatment based on one or more of the first set of fNIRS or the second set of fNIRS (page 8, paras. 4-5, “hypothetical fNIRS measurement intensity of the stimulation is the period of time x, after calculating each 15 s period of hemoglobin oxygenation and percentage PerOxy and PerDeoxy the energy of the initial energy of deoxygenated hemoglobin, Per=max (PerOxy, PerDeoxy), Per PerOxy and PerDeoxy maximum value; step 2, according to stimulation mode of the Per value after determining”); and
provide control feedback to the TMS device or visualization to a display to adjust one or more parameters or localization of the TMS treatment based on the applied dosing (page 7, para. 7, “the display and control module can see the current stimulation parameters, such as manual/automatic mode selection, resting the motion threshold, current stimulation intensity, stimulation frequency and stimulation time, and can change parameter by LCD touch screen key module, so as to fNIRS signal through real time control the TMS stimulation”).
Tan et al. fails to teach wherein execution of the instructions by the processor causes the processor to: receive a first set of fNIRS measurements of a treatment region in response to a TMS treatment applied by the TMS device to the treatment region of a patient.
Kozel et al. teaches an analogous fNIRS-TMS system and method wherein a first set of fNIRS measurements of a treatment region are received in response to a TMS treatment applied by the TMS device to the treatment region of a patient (see Annotated Figure 2; page 4, para. 6, “fNIRS data was acquired one minute prior to stimulation, during the 15 stimulation/rest epochs (90 seconds per epoch), and during a one-minute poststimulation period resulting in a total recording time of 24 minutes and 30 seconds”).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the system of Tan et al. with the first set of fNIRS measurements of a treatment region in response to a TMS treatment applied by the TMS device of Kozel et al. fNIRS data acquired in response to a TMS treatment may be employed to conduct a comparative analysis between the brain’s hemodynamic changes associated with TMS of the motor cortex and the prefrontal cortex. Furthermore, fNIRS measurements collected during stimulation may provide insights into the effectiveness of the stimulation parameters and the localization of TMS stimulation (Kozel et al., page 4, para. 6, “After the fNIRS recording was complete, the location of the TMS stimulation relative to the fNIRS system was determined”; page 7, para. 3, “the conditions studied (healthy participants stimulated for 10 secs with 1 Hz rTMS), the brain changes associated with motor cortex stimulation and prefrontal cortex stimulation”; page 7, para. 6, “Gaining a better understanding of how different treatment parameters interact to produce clinical outcome is critical to optimizing the effectiveness of these new treatments”).
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Annotated Figure 2
Regarding claim 19, Tan et al., in view of Kozel et al., teaches the non-transitory computer-readable medium according to claim 18 as stated above wherein the instruction further causes the processor to provide control feedback to the TMS device (Tan et al., page 5, para. 12, “said analyzing control device connected with the TMS stimulation system and fNIRS signal acquisition system”) or visualization to the display to adjust one or more of: a coil to treatment region distance, a gyrus orientation, an excitability output, a location of the TMS treatment, a frequency of the TMS treatment (Tan et al., Fig. 3; page 8, para. 3, “the working method of the analyzing control device, comprising:” and paras. 5-6, “changing the stimulation intensity [via an adjusting formula] …the same treatment/[formula] [applies] for the stimulation frequency”), a duration of the TMS treatment, an effectiveness of treatment region changes based on the TMS treatment, or a stopping criteria for the TMS treatment.
Regarding claim 20, Tan et al., in view of Kozel et al., teaches the non-transitory computer-readable medium according to claim 18 as stated above.
Tan et al. further teaches wherein the control feedback to the TMS device or visualization to the display is to provide sufficient cortical excitability for neurological treatment (page 1, para. 6, “technical field of nerve disease treatment and brain function research”; page 6, para. 4, “analyzing control device automatically sends stimulation parameter to a transcranial magnetic stimulation system”; page 7, para. 7, “stimulation coil driven by TMS stimulation system, for magnetic stimulation to the cortex of the brain”).
Tan et al. fails to teach wherein the TMS treatment is for treatment of depression, and the treatment region is the prefrontal cortex.
Kozel et al. teaches an analogous fNIRS-TMS system and method wherein the TMS treatment is for treatment of depression (page 8, para. 1, “relieve the depressive symptoms”; page 2, para. 2, “daily prefrontal rTMS has been found to have antidepressant properties when treating patients with depression”), the treatment region is the prefrontal cortex (page 5, para. 1, “The fNIRS probes were positioned over the prefrontal cortex (see Figure 1) – defined as 5 cm anterior to the motor cortex position in a para-sagittal line…the coil was moved 5 cm anteriorly in a para-sagittal line. The fNIRS recording and TMS stimulation were exactly the same as for the motor cortex stimulation”).
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the non-transitory computer-readable medium for a transcranial magnetic stimulation (TMS) functional Near-Infrared Spectroscopy (fNIRS) (TMS-fNIRS) system of Tan et al. with the TMS treatment for treatment of depression wherein the treatment region is the prefrontal cortex of Kozel et al. Transcranial magnetic stimulation is an non-invasive therapy proven effective in treating a multitude of neuropsychiatric disorders and diseases; therefore, it would be beneficial to include a treatment region to the prefrontal cortex, where TMS has demonstrated antidepressive properties (Kozel et al., page 2, para. 1, “Transcranial magnetic stimulation (TMS) is a technology that is being used to investigate normal brain function and various neuropsychiatric disorders…”; page 2, para. 2, “rTMS is being investigated as a possible treatment for various brain disorders. As an example, daily prefrontal rTMS has been found to have antidepressant properties when treating patients with depression…”).
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tan et al., in view of Kozel et al. as applied to claim 14 above, further in view of Jiang et al.
Regarding claim 16, Tan et al., in view of Kozel et al., teaches the system according to claim 14 as stated above. Tan et al., in view of Kozel et al., fails to teach wherein the TMS device is configured to generate at least one of: a 12-block sequence of 1 Hz stimulation with 4 sec on and off 26 sec, a 12-block sequence of 10 Hz stimulation with 4 sec on and off 26 sec; or a 48-jittered single pulses stimulation sequence.
Jiang et al. teaches an analogous system and method for TMS treatment wherein the TMS device is configured to generate at least one of: a 12-block sequence of 1 Hz stimulation with 4 sec on and off 26 sec, a 12-block sequence of 10 Hz stimulation with 4 sec on and off 26 sec (page 5, Figure 2, “Ten hertz stimulation was performed for 4 s followed by 26 s of rest for a total of 12 epochs”); or a 48-jittered single pulses stimulation sequence.
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the system of Tan et al., in view of Kozel et al., with the TMS device configured to generate a 12-block sequence of 10 Hz stimulation with 4 seconds on and off 26 seconds of Jiang et al. Implementing a ten hertz stimulation with four second duration per session, constitutes a standard treatment protocol for transcranial magnetic stimulation (TMS) (Jiang et al., page 2, para. 6, “All rTMS treatments were performed with a Neurostar TMS Therapy System (Neuronet ics, Inc., Malvern, PA, USA). Stimulation protocol was followed per the product documentation…”; page 7, para. 2, “10 Hz stimulation has been shown to increase [HbO], which was associated with continued therapeutic effects of TMS”).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mishelevich et al. (US 2011/0082326) discloses a TMS treatment for depression wherein a coil array simultaneously stimulates the dorsal prefrontal cortex, orbito-Frontal Cortex, and subgenual cingulate. Nahas et al. (2001) discloses a study wherein the left dorsolateral prefrontal cortex was stimulated via a TMS coil and the changes in blood flow in the prefrontal cortex near the stimulation site was analyzed. Shinba et al. discloses an TMS-NIRS system wherein over the course of TMS treatment frontal cerebral hemoglobin concentrations were monitored. Additionally, Shinba et al. study discloses one light source and detector which differs from the claimed invention.
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/B.R.L./Examiner, Art Unit 3791 /JENNIFER ROBERTSON/Supervisory Patent Examiner, Art Unit 3791
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