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 .
Response to Arguments
Applicant’s arguments with respect to the rejection of Independent Claim 1 under 35 U.S.C. 103 as being unpatentable over US 2020/0129757 A1 to Xiao (“Xiao”) in view of WO 2020/206387 A1 to Harkema et al. (“Harkema”) have been considered and are persuasive. The Examiner agrees that the combination of Xiao and Harkema does not teach such determining “based on at least one of (i) spatial information of the lead or (ii) physiological information sensed by the plurality of electrodes” as recited by amended Claim 1. Therefore, the rejection is withdrawn. However, upon further consideration, new grounds of rejection is made in view of US 2021/0339024 A1.
Applicant’s arguments with respect to the rejection of Independent Claim 15 under 35 USC 103 are similar to Applicant’s arguments regarding Claim 1. Applicant’s arguments have been fully considered and are persuasive for the same reasons as explained above with respect to Claim 1. Therefore, the rejection is withdrawn. However, upon further consideration, new grounds of rejection is made in view of US 2021/0339024 A1.
Applicant’s arguments regarding the rejection of dependent Claims 3-14 and 17-22 under 35 USC 103 are based on Applicant’s arguments regarding Claims 1 and 15. Applicant’s arguments have been fully considered and are persuasive for the same reasons as explained above. Therefore, the rejection is withdrawn. However, upon further consideration, new grounds of rejection is made in view of US 2021/0339024 A1
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.
Claims 1 and 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over previously cited US 2020/0129757 A1 to Xiao (“Xiao”) in view of WO 2020/206387 A1 to Harkema et al. (“Harkema”) and US 20210339024 A1 to Naor et al. (“Naor”).
Regarding Independent Claim 1, Xiao discloses:
A system for providing electrostimulation to a patient, comprising: (Abstract, “Techniques are disclosed to automate determination of therapy parameter values for adaptive deep brain stimulation (aDBS);” Para. [0007], “In one example, this disclosure describes a system comprising a medical device comprising a memory and processing circuitry. The processing circuitry is configured to determine a present power value of power in a frequency band in a bioelectric signal, generated in a brain….”);
an implantable stimulator configured to provide electrostimulation to a neural target of the patient via a lead comprising a plurality of electrodes; (Para. [0018], “FIG. 1 is a conceptual diagram illustrating an example system 100 that includes an implantable medical device (IMD) 106 configured to deliver adaptive deep brain stimulation to a patient 112.”);
and a programming device communicatively coupled to the implantable stimulator, the programming device including a controller (Para. [0041], “External programmer 104 wirelessly communicates with IMD 106 as needed to provide or retrieve therapy information.”);
configured to: determine a search space of electrode configurations and parameter values for the lead with respect to the neural target …, the search space including a subset of the plurality of electrodes for delivering stimulation and stimulation parameter values or value ranges associated with the subset of electrodes;” (Para. [0044], “IMD 106 or programmer 104 (e.g., a medical device), alone or in combination, may automatically determine electrode configuration and therapy parameters. For example, the medical device may determine which electrodes to use for stimulation based on which electrodes are most proximal to the LFP source. As described in more detail, the medical device may also titrate the amplitude or another parameter of the stimulation to automatically determine the stimulation amplitude.”);
Xiao’s “determin[ing] which electrodes to use for stimulation based on which electrodes are most proximal to the LFP source” is such “determin[ing] a search space of electrode configurations” as claimed when the term is afforded its broadest reasonable interpretation.
Xiao’s “titrat[ing] the amplitude or another parameter of the stimulation to automatically determine the stimulation amplitude” is such “determin[ing] a search space of … parameter values for the lead with respect to the neural target” as claimed when the term is afforded its broadest reasonable interpretation.
This interpretation would merit reconsideration were the term “search space” to be more precisely defined.
More specifically, Claim 1 requires that the recited search space “includ[e] a subset of electrodes.” This is quite broad.
under a first patient state, evaluate a clinical response indicator responsive to electrostimulation delivered using electrodes and stimulation parameter values within the determined search space, and determine at least one base stimulation setting corresponding to the clinical response indicator satisfying a specific condition, the at least one base stimulation setting including an optimal electrode configuration and an optimal stimulation parameter value; (Para. [0056], “…in response to delivery of a present electrical stimulation (e.g., using electrodes 116, 118 selected based on the CSD values) having a present therapy parameter value, IMD 106 may determine a present power value of power in a frequency band (e.g., beta band) in the bioelectric signal generated by the LFP source and sensed by sense electrodes. … if the difference between the present power value and the previous power value is less than a threshold value (e.g., 0.5 uV/√{square root over (Hz)} as one non-limiting example), further adjustment of the therapy value may not provide noticeably more effective therapy.”).
Xiao’s “present” state (i.e., “a present electrical stimulation,” “a present therapy parameter value,” etc.) is such a “first patient state” as claimed when the term is afforded its broadest reasonable interpretation.
Xiao’s use of “the difference between the present power value and the previous power value” to determine whether “further adjustment of the therapy value” will “provide noticeably more effective therapy” is such “evaluat[ing] a clinical response indicator responsive to electrostimulation delivered using electrodes and stimulation parameter values within the identified search space” when the term is afforded its broadest reasonable interpretation.
Xiao’s “difference” is such a clinical response indicator as claimed.
Xiao’s “determin[ing] a present power value of power in a frequency band” is such “determin[ing] at least one base stimulation setting corresponding to the clinical response indicator satisfying a specific condition” as claimed when the term is afforded its broadest reasonable interpretation.
Xiao’s “base stimulation setting” includes “an optimal electrode configuration and an optimal stimulation parameter value” because:
Xiao’s “present power value” is based on Xiao’s CSD values (see, e.g., Xiao at Para. [0083] elaborating on CSD values, “To determine which electrodes 116, 118 to use for delivering electrical stimulation, processing circuitry 210 may determine which electrodes 116, 118 have the greatest current source density (CSD) value due to sensing of the LFP signal from the LFP source.”), and thus includes “an optimal electrode configuration;” and
Xiao’s “present power value” is based on Xiao’s “present therapy parameter value” (see, e.g., Xiao at Para. [0015] elaborating on therapy parameter values, “This disclosure describes example techniques to automatically determine values of electrical stimulation therapy parameters, such as electrical stimulation amplitude values…;” see also Xiao at Para. [0065], “An example range of electrical stimulation parameters believed to be effective in DBS to manage a movement disorder of patient include…”), and thus includes “an optimal stimulation parameter value.”
This interpretation would merit reconsideration were the terms “clinical response indicator” and “satisfying a specific condition” defined more precisely in the claim.
and store in a memory the determined search space and the at least one base stimulation setting associated with the corresponding clinical response indicator (Para. [0062], “…memory 211 stores therapy programs 214, previous power value 216, and sense electrode combinations and associated stimulation electrode combinations 218, in separate memories within memory 211 or separate areas within memory 211. Each stored therapy program 214 defines a particular set of electrical stimulation parameters (e.g., a therapy parameter set), such as a stimulation electrode combination, electrode polarity, current or voltage amplitude, pulse width, and pulse rate.”).
and a therapy titration user interface device … configured to: under a second patient state different from the first patient state, evaluate the clinical response indicator responsive to electrostimulation in accordance with the at least one base stimulation setting; (Para. [0017], “The IMD or programmer may titrate one or more of the therapy parameters using various example techniques. As one example, the amplitude of the stimulation therapy is gradually adjusted (e.g., increased) until a difference in a current beta band signal power a previous beta band signal power, e.g., obtained from local field potential (LFP) signals, is less than a predetermined threshold difference value, or until the patient experiences undesirable side effects.”);
As explained above, the term “therapy titration user interface device” is being interpreted in accordance with Applicant’s characterization and with Para. [0109] of the Present Specification to recite a broad genus of devices having a structure which allows a user to interact with the device, the intended use of which device is therapy titration.
Xiao’s programmer is such a device (see Xiao at Para. [0041], “…programmer 104 may be a patient programmer that allows patient 112 to select programs and/or view and modify therapy parameters…”).
Xiao uses a single device to carry out both Xiao’s therapy titration function and Xiao’s “programming device” functions. This deficiency is cured by Harkema, as explained below.
modify the clinical response indicator based on a comparison between the clinical response indicator under the second patient state and the clinical response indicator under the first patient state; (Para. [0058], “… if the difference is greater than a threshold value, the medical device may iteratively adjust the present therapy parameter value and deliver electrical stimulation with the adjusted parameter value until the difference between the present power value (e.g., power value of the power in the frequency band in the current iteration) and the previous power value (e.g., power value of the power in the frequency band in the previous iteration) is less than the threshold value. Once the difference becomes less than the threshold value, the medical device may cease adjustment of the present therapy parameter value and set a final therapy parameter value equal to the present therapy parameter value.”);
As explained above, Xiao’s “difference” is such a “clinical response indicator” as claimed.
Xiao modifies Xiao’s “difference” by “iteratively adjust[ing] the present therapy parameter value and deliver electrical stimulation with the adjusted parameter value until the difference between the present power value … and the previous power value … is less than the threshold value.” This modification is “based on a comparison between the clinical response indicator under the second patient state and the clinical response indicator under the first patient state” as claimed (as Xiao’s modification is done relative to a threshold).
modify the at least one base stimulation setting by iteratively adjusting the optimal electrode configuration or the optimal stimulation parameter value within the search space previously determined by the programming device and stored in the memory until the modified clinical response indicator satisfies a specific condition under the second patient state; (Para. [0058], “… if the difference is greater than a threshold value, the medical device may iteratively adjust the present therapy parameter value and deliver electrical stimulation with the adjusted parameter value until the difference between the present power value (e.g., power value of the power in the frequency band in the current iteration) and the previous power value (e.g., power value of the power in the frequency band in the previous iteration) is less than the threshold value. Once the difference becomes less than the threshold value, the medical device may cease adjustment of the present therapy parameter value and set a final therapy parameter value equal to the present therapy parameter value.”);
Xiao’s “base stimulation setting” is based on Xiao’s “present therapy parameter value” (see, e.g., Xiao at Para. [0015] elaborating on therapy parameter values, “This disclosure describes example techniques to automatically determine values of electrical stimulation therapy parameters, such as electrical stimulation amplitude values…;” see also Xiao at Para. [0065], “An example range of electrical stimulation parameters believed to be effective in DBS to manage a movement disorder of patient include…”), which Xiao states at Para. [0058] to be adjusted during Xiao’s titration.
“store in the memory the modified at least one base stimulation setting associated with the modified clinical response indicator;” (Para. [0079], “The updates to the therapy programs may be stored within therapy programs 214 portion of memory 211.”)
“and generate a control signal to the implantable stimulator and cause delivery of electrostimulation to the neural target in accordance with the modified at least one base stimulation setting.” (Para. [0058], “The medical device may cause delivery of electrical stimulation having the final therapy parameter value.”).
Xiao differs from the invention of Claim 1 in that Xiao performs the functions of both the “therapy titration user interface device” and the “programming device” via a single device (i.e., Xiao’s “programmer”).
Thus, Xiao does not disclose:
based on at least one of (i) spatial information of the lead or (ii) physiological information sensed by the plurality of electrodes,
a therapy titration user interface device, different and separate from the programming device and communicatively coupled to the implantable stimulator
That is, Xiao’s “therapy titration user interface device” is not “different and separate from the programming device and communicatively coupled to the implantable stimulator”
Harkema describes a “closed loop system for control of spinal cord epidural stimulation” (Abstract). Harkema is analogous art.
Harkema teaches the use of two systems analogous to the recited “programming device” and “therapy titration user interface device” that cooperate with one another to achieve similar results via different methodology. Harkema’s analogous use of two such systems remedies that deficiency of Xiao.
Accordingly, Harkema discloses:
“a therapy titration user interface device, different and separate from the programming device and communicatively coupled to the implantable stimulator” (Paras. [0014] and [0015]; Fig. 1, “second controller 16;” “Line A,” “Line B,” Line C” and “Line D” show such “communicative coupling” as claimed)
Harkema uses a “first controller 14” and “second controller 16” to perform functions similar to the recited “programming device” and “therapy titration user interface device.”
Harkema’s “first controller 14” is “a neurostimulator controller, such as a Medtronic™ Intellis™ clinician programmer or MyStim™ programmer” (Harkema at Para. [0014]), and is similar to the recited “programming device.”
Harkema’s “second controller 16” is “a mobile device, such as a smartphone, tablet computer, or other portable computing device including a processor, a non-transitory computer readable storage medium, and means for electronic communication to and from the second controller” (Harkema at Para. [0014]). Harkema’s “second controller 16” contains software that “applies a predictive learning algorithm 30 to identify optimal stimulation configurations for neuromodulation” (Harkema at Para. [0015]), and is akin to the recited “titration therapy device.
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Xiao with the teachings of Harkema (i.e., to modify the device of Xiao such that Xiao’s “therapy titration user interface device” is different and separate from Xiao’s programming device and communicatively coupled to Xiao’s implantable stimulator in the manner of Harkema’s “second controller 16” and “first controller 14”) in order to “generate complex multi-system stimulation patterns in real-time … for improving regulation and function” (Harkema at Para. [0003]).
Naor describes “A method for selecting stimulation treatment parameter values…” (Abstract). Naor is analogous art.
Naor teaches:
based on at least one of (i) spatial information of the lead or (ii) physiological information sensed by the plurality of electrodes, (Abstract, “A method for selecting stimulation treatment parameter values, including: receiving signals related to a patient condition from at least one sensor, during and/or following at least one brain stimulation session, in which stimulation is delivered in at least one location within the brain, using at least one set of treatment parameter values; analyzing the received signals to quantitatively assess at least one treatment side effect and at least one symptomatic effect; selecting a set of treatment parameter values based on the quantitative assessment of the treatment side effects and the symptomatic effect.”).
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of combined Xiao and Harkema with the teachings of Naor (i.e., to use such physiological information sensed by the plurality of electrodes as the basis of Xaio’s search space determination) in order to facilitate treatment that aligns with symptom level, change in symptom level, side effect level and change in side effect level (Naor at Para. [0133]).
Regarding Claim 3, the combination of Xiao, Harkema and Noar renders obvious the entirety of Claim 1 as explained above.
Xiao additionally discloses:
wherein the therapy titration user interface device is a mobile device operable by the patient and coupled to the implantable stimulator via a wireless link (Para. [0109], “In general, programmer 104 comprises any suitable arrangement of hardware, alone or in combination with software and/or firmware, to perform the techniques attributed to programmer 104, and processing circuitry 310, user interface 302, and telemetry circuitry 308 of programmer 104. In various examples, programmer 104 may include one or more processors, which may include fixed function processing circuitry and/or programmable processing circuitry, as formed by, for example, one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components. Programmer 104 also, in various examples, may include a memory 311, such as RAM, ROM, PROM, EPROM, EEPROM, flash memory, a hard disk, a CD-ROM, comprising executable instructions for causing the one or more processors to perform the actions attributed to them. Moreover, although processing circuitry 310 and telemetry circuitry 308 are described as separate modules, in some examples, processing circuitry 310 and telemetry circuitry 308 may be functionally integrated with one another. In some examples, processing circuitry 310 and telemetry circuitry 308 correspond to individual hardware units, such as ASICs, DSPs, FPGAs, or other hardware units;” Para. [0041], “External programmer 104 wirelessly communicates with IMD 106 as needed to provide or retrieve therapy information. Programmer 104 is an external computing device that the user, e.g., a clinician and/or patient 112, may use to communicate with IMD 106. For example, programmer 104 may be a clinician programmer that the clinician uses to communicate with IMD 106 and program one or more therapy programs for IMD 106. Alternatively, programmer 104 may be a patient programmer that allows patient 112 to select programs and/or view and modify therapy parameters;” Para. [0079], “Telemetry circuitry 208 supports wireless communication between IMD 106 and an external programmer 104 or another computing device under the control of processing circuitry 210.”).
Regarding Claim 4, the combination of Xiao, Harkema and Naor renders obvious the entirety of Claim 1 as explained above.
Xiao additionally discloses:
wherein the therapy titration user interface device includes a user interface configured to display graphically the determined search space and to receive user input to modify the at least one base stimulation setting (Para. [0111], “User interface 302 may include a button or keypad, lights, a speaker for voice commands, a display, such as a liquid crystal (LCD), light-emitting diode (LED), or organic light-emitting diode (OLED). In some examples the display may be a touch screen. User interface 302 may be configured to display any information related to the delivery of stimulation therapy, identified patient behaviors, sensed patient parameter values, patient behavior criteria, or any other such information. User interface 302 may also receive user input via user interface 302. The input may be, for example, in the form of pressing a button on a keypad or selecting an icon from a touch screen;” Para. [0041], “Programmer 104 may also provide an indication to patient 112 when therapy is being delivered, when patient input has triggered a change in therapy or when the power source within programmer 104 or IMD 106 needs to be replaced or recharged. For example, programmer 104 may include an alert LED, may flash a message to patient 112 via a programmer display, generate an audible sound or somatosensory cue to confirm patient input was received, e.g., to indicate a patient state or to manually modify a therapy parameter.”).
Claims 5-12 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over previously cited US 2020/0129757 A1 to Xiao (“Xiao”) in view of WO 2020/206387 A1 to Harkema et al. (“Harkema”) and US 20210339024 A1 to Naor et al. (“Naor”) as applied to Claim 1 above, and further in view of previously cited US 2009/0287273 A1 to Carlton et al. (“Carlton”).
Regarding Claim 5, the combination of Xiao, Harkema and Naor renders obvious the entirety of Claim 4 as explained above.
The combination of Xiao, Harkema and Naor does not disclose:
wherein the user interface is configured to display graphically the identified search space as a heatmap depicting intensities of clinical responses to electrostimulation over a range of electrode positions on the lead and a range of stimulation parameter values
Carlton describes “A therapy tracking system and method [which includes] a processor that obtains physiological information regarding a patient and a time period during which a deep brain stimulation (DBS) therapy is conducted.” Carlton is analogous art.
Carlton discloses:
wherein the user interface is configured to display graphically the identified search space as a heatmap depicting intensities of clinical responses to electrostimulation over a range of electrode positions on the lead and a range of stimulation parameter values (Para. [0202], “…the system is configured to identify overlapping beneficial and/or adverse regions in a similar manner. For example, the system may store information regarding one or more benefits or side effects with respect to structures in an atlas or map, such that when those structures are stimulated, the stimulation may cause certain therapeutic benefits and/or side effects. This benefit/side effect atlas or map can be stored and shown in two or three dimensions. In certain examples, different benefits or side effects can be identified by a display using different color coded structures or substructures, different intensity patterns, different hatching patterns, via text on screen, etc., as shown in FIGS. 3 e-3 f, in which overlapping areas between a VOA and an anatomical structure or substructure are highlighted in different ways.”).
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of combined Xiao, Harkema and Naor with the teachings of Carlton (i.e., to implement with the system of combined Xiao, Harkema and Naor such a system to “produce visual aids that help in a DBS parameter selection process” as that disclosed by Carlton) in order to tailor the DBS parameters (such as which one or more of the stimulating electrode contacts to use, the stimulation pulse amplitude, the stimulation pulse width, and/or the stimulation frequency) for a particular patient to improve the effectiveness of the DBS therapy” (Carlton at Para. [0012] and Para. [0013]).
Regarding Claim 6, the combination of Xiao, Harkema and Naor renders obvious the entirety of Claim 1 as explained above.
The combination of Xiao, Harkema and Naor does not disclose:
wherein the controller is configured to evaluate the clinical response indicator using one or more clinical effects responsive to electrostimulation delivered using electrodes and stimulation parameter values within the determined search space.
Carlton describes “A therapy tracking system and method [which includes] a processor that obtains physiological information regarding a patient and a time period during which a deep brain stimulation (DBS) therapy is conducted.” Carlton is analogous art.
Carlton discloses:
wherein the controller is configured to evaluate the clinical response indicator using one or more clinical effects responsive to electrostimulation delivered using electrodes and stimulation parameter values within the determined search space (Paras. [0349] through [0357], “8. based on the noted benefits and side effects relative to the various tested VOAs, the system determines and displays: a. a new target stimulation volume for each benefit individually; b. a collective target stimulation volume that incorporates an addition of all the volumes of step 8(a); c. side effect volumes for each individual side effect; and/or d. a collective side effect volume that incorporates the addition of all side effects volumes of step 8(c); 9. the system estimates and outputs: a. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a specific benefit; and b. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a collective therapy where: i. for example in Parkinson's, a particular benefit such as tremor may be weighted differently than rigidity, the goal of the stimulation settings being to optimize the total benefit to the patient;…”)
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of combined Xiao, Harkema and Naor with the teachings of Carlton (i.e., to refine Xiao’s “clinical response indicator” such that it incorporates Carlton’s evaluation of the clinical response indicator using one or more clinical effects responsive to electrostimulation) in order “to tailor the DBS parameters (such as which one or more of the stimulating electrode contacts to use, the stimulation pulse amplitude, the stimulation pulse width, and/or the stimulation frequency) for a particular patient to improve the effectiveness of the DBS therapy” (Carlton at Para. [0012]).
Regarding Claim 7, the combination of Xiao, Harkema, Naor and Carlton renders obvious the entirety of Claim 6 as explained above.
Carlton additionally discloses:
wherein: the controller is configured to evaluate the clinical response indicator using a combination of the one or more clinical effects each weighted by respective weight factors; and the therapy titration user interface device is configured to, based on the comparison between the clinical response indicator under the second patient state and the clinical response indicator under the first patient state, identify one or more of the clinical effects that have worsened from the first patient state to the second patient state, (Para. [0221], “FIG. 3 j illustrates generally an example of displaying prior stimulation areas in two or three dimensions as well as indicating (e.g., labeled via color, texture, size, etc.) those stimulation areas that have been associated with one or more side effects. In the example of FIG. 3 j, the side effect areas are displayed in yellow outside of the currently represented VOA. … This may be helpful to the user by indicating those areas which may be stimulated without causing a side effect. A user may thereby determine areas in which to avoid stimulation;” Para. [0224], “In an example, for any one or more of the molds, the side effects can be distinguished as having varying levels of effect or severity. In other examples, one or more structures can be identified in relation to a benefit or side effect, in conjunction with, or instead of its anatomical name. In an example, the label (e.g., a color, a shade, etc.) of a structure can be affected by a degree or severity of the benefit or side effect. In an example, the greater the benefit or the worse the side effect, the darker or lighter the color or shading;” Para. [0314], “A clinician may subsequently test the system-suggested parameters or similar parameters, and adjust the parameters using some of the methods described above, since the resulting benefits and side effects may be different than those anticipated by the system.”);
and to modify the clinical response indicator by increasing respective weight factors for the identified one or more clinical effects (Paras. [0349] through [0357], “8. based on the noted benefits and side effects relative to the various tested VOAs, the system determines and displays: a. a new target stimulation volume for each benefit individually; b. a collective target stimulation volume that incorporates an addition of all the volumes of step 8(a); c. side effect volumes for each individual side effect; and/or d. a collective side effect volume that incorporates the addition of all side effects volumes of step 8(c); 9. the system estimates and outputs: a. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a specific benefit; and b. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a collective therapy where: i. for example in Parkinson's, a particular benefit such as tremor may be weighted differently than rigidity, the goal of the stimulation settings being to optimize the total benefit to the patient;…”).
Regarding Claim 8, the combination of Xiao, Harkema, Naor and Carlton renders obvious the entirety of Claim 6 as explained above.
Carlton additionally discloses:
wherein the one or more clinical effects include one or more motor symptoms including bradykinesia, tremor, or rigidity. (Paras. [0349] through [0357], “8. based on the noted benefits and side effects relative to the various tested VOAs, the system determines and displays: a. a new target stimulation volume for each benefit individually; b. a collective target stimulation volume that incorporates an addition of all the volumes of step 8(a); c. side effect volumes for each individual side effect; and/or d. a collective side effect volume that incorporates the addition of all side effects volumes of step 8(c); 9. the system estimates and outputs: a. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a specific benefit; and b. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a collective therapy where: i. for example in Parkinson's, a particular benefit such as tremor may be weighted differently than rigidity, the goal of the stimulation settings being to optimize the total benefit to the patient;…”).
Regarding Claim 9, the combination of Xiao, Harkema, Naor and Carlton renders obvious the entirety of Claim 6 as explained above.
Carlton additionally discloses:
wherein the therapy titration user interface device is configured to receive a user input of the one or more clinical effects (Para. [0021], “The at least one of the side effect and the benefit may be received as user input via a user interface of the system. For example, the physician may observe and enter into the system certain benefits and/or side effects resulting from a stimulation using a certain set of stimulation parameters.”).
Regarding Claim 10, the combination of Xiao, Harkema, Naor and Carlton renders obvious the entirety of Claim 6 as explained above.
Carlton additionally discloses:
wherein the therapy titration user interface device includes, or is communicatively coupled to, one or more sensors to sense the one or more clinical effects (Para. [00374], “In an example embodiment of the present invention, the system is configured to include data input or data analysis capabilities. In an example, the system includes one or more sensors used for the data input or analysis capabilities. In an example embodiment, the system is configured to receive information from at least one sensor or other instrument coupled to the clinician programmer system;” see also Paras. [0375] through [0379]).
Regarding Claim 11, the combination of Xiao, Harkema and Naor discloses the entirety of Claim 1 as explained above.
Xiao additionally discloses:
wherein the controller is configured to determine, and store in the memory, a plurality of base stimulation settings each associated with respective clinical response indicators, … the plurality of base stimulation settings each including respective optimal electrode configurations and respective optimal stimulation parameter values (Para. [0062], “In the example shown in FIG. 2, memory 211 stores therapy programs 214, previous power value 216, and sense electrode combinations and associated stimulation electrode combinations 218, in separate memories within memory 211 or separate areas within memory 211. Each stored therapy program 214 defines a particular set of electrical stimulation parameters (e.g., a therapy parameter set), such as a stimulation electrode combination, electrode polarity, current or voltage amplitude, pulse width, and pulse rate.”);
Xiao’s above-indicated items are “each associated with” Xiao’s clinical response indicators.
The combination of Xiao, Harkema and Naor does not disclose:
the respective clinical response indicators each evaluated under the first patient state using one or more clinical effects weighted by respective weight factors,
Carlton describes “A therapy tracking system and method [which includes] a processor that obtains physiological information regarding a patient and a time period during which a deep brain stimulation (DBS) therapy is conducted.” Carlton is analogous art.
Carlton discloses:
the respective clinical response indicators each evaluated under the first patient state using one or more clinical effects weighted by respective weight factors, (Para. [0221], “FIG. 3 j illustrates generally an example of displaying prior stimulation areas in two or three dimensions as well as indicating (e.g., labeled via color, texture, size, etc.) those stimulation areas that have been associated with one or more side effects. In the example of FIG. 3 j, the side effect areas are displayed in yellow outside of the currently represented VOA. … This may be helpful to the user by indicating those areas which may be stimulated without causing a side effect. A user may thereby determine areas in which to avoid stimulation;” Para. [0224], “In an example, for any one or more of the molds, the side effects can be distinguished as having varying levels of effect or severity. In other examples, one or more structures can be identified in relation to a benefit or side effect, in conjunction with, or instead of its anatomical name. In an example, the label (e.g., a color, a shade, etc.) of a structure can be affected by a degree or severity of the benefit or side effect. In an example, the greater the benefit or the worse the side effect, the darker or lighter the color or shading;” Para. [0314], “A clinician may subsequently test the system-suggested parameters or similar parameters, and adjust the parameters using some of the methods described above, since the resulting benefits and side effects may be different than those anticipated by the system;” Paras. [0349] through [0357], “8. based on the noted benefits and side effects relative to the various tested VOAs, the system determines and displays: a. a new target stimulation volume for each benefit individually; b. a collective target stimulation volume that incorporates an addition of all the volumes of step 8(a); c. side effect volumes for each individual side effect; and/or d. a collective side effect volume that incorporates the addition of all side effects volumes of step 8(c); 9. the system estimates and outputs: a. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a specific benefit; and b. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a collective therapy where: i. for example in Parkinson's, a particular benefit such as tremor may be weighted differently than rigidity, the goal of the stimulation settings being to optimize the total benefit to the patient;…”).
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of combined Xiao, Harkema and Naor with the teachings of Carlton (i.e., to refine Xiao’s “clinical response indicator” such that it incorporates Carlton’s weighting of clinical effects by respective weight factors for the identified clinical effects) in order “to tailor the DBS parameters (such as which one or more of the stimulating electrode contacts to use, the stimulation pulse amplitude, the stimulation pulse width, and/or the stimulation frequency) for a particular patient to improve the effectiveness of the DBS therapy” (Carlton at Para. [0012]).
Regarding Claim 12, the combination of Xiao, Harkema, Naor and Carlton renders obvious the entirety of Claim 11 as explained above.
Carlton additionally discloses:
wherein the controller is configured to evaluate one or more of the plurality of clinical response indicators using weighted combinations of one or more clinical effects each weighted by respective weight factors, the weight factors associated with one of the plurality of base stimulation settings being different from the weight factors associate with another of the plurality of base stimulation settings (Para. [0356] to [0357], “b. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a collective therapy where: i. for example in Parkinson's, a particular benefit such as tremor may be weighted differently than rigidity, the goal of the stimulation settings being to optimize the total benefit to the patient;…”).
Regarding Claim 14, the combination of Xiao, Harkema, Naor and Carlton renders obvious the entirety of Claim 11 as explained above.
Xiao additionally discloses:
wherein the therapy titration user interface device is configured to: under a second patient state different from the first patient state, evaluate respective clinical response indicators responsive to electrostimulation in accordance with the plurality of base stimulation settings; (Para. [0017], “The IMD or programmer may titrate one or more of the therapy parameters using various example techniques. As one example, the amplitude of the stimulation therapy is gradually adjusted (e.g., increased) until a difference in a current beta band signal power a previous beta band signal power, e.g., obtained from local field potential (LFP) signals, is less than a predetermined threshold difference value, or until the patient experiences undesirable side effects.”);
based on a comparison between the clinical response indicators under the second patient state and the clinical response indicators under the first patient state, select a base stimulation setting from the plurality of base stimulation settings; (Para. [0063], “Previous power value 216 is indicative of a power level of power in a frequency band of a bioelectric signal generated in response to delivery of a previous electrical stimulation having a previous therapy parameter value different than the present therapy parameter value. As described in more detail, in some examples, IMD 106 may determine a difference between previous power value 216 and the present power value to determine whether further adjustment to a therapy parameter value is needed as a way to automatically titrate to the therapy parameter to an appropriate value.”);
modify the selected base stimulation setting by iteratively adjusting an optimal electrode configuration or an optimal stimulation parameter value of selected base stimulation setting within the determined search space until the clinical response indicator associated with the selected base stimulation setting satisfies a specific condition under the second patient state; (Para. [0058], “… if the difference is greater than a threshold value, the medical device may iteratively adjust the present therapy parameter value and deliver electrical stimulation with the adjusted parameter value until the difference between the present power value (e.g., power value of the power in the frequency band in the current iteration) and the previous power value (e.g., power value of the power in the frequency band in the previous iteration) is less than the threshold value. Once the difference becomes less than the threshold value, the medical device may cease adjustment of the present therapy parameter value and set a final therapy parameter value equal to the present therapy parameter value.”);
store in the memory the modified selected base stimulation setting; (Para. [0079], “The updates to the therapy programs may be stored within therapy programs 214 portion of memory 211.”);
and generate a control signal to the implantable stimulator to deliver electrostimulation in accordance with the modified selected base stimulation setting (Para. [0058], “The medical device may cause delivery of electrical stimulation having the final therapy parameter value.”).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over previously cited US 2020/0129757 A1 to Xiao (“Xiao”) in view of WO 2020/206387 A1 to Harkema et al. (“Harkema”), US 20210339024 A1 to Naor et al. (“Naor”) and previously cited US 2009/0287273 A1 to Carlton et al. (“Carlton”) as applied to Claim 11 above, and further in view of previously cited US 2021/0085257 A1 to Patil et al. (“Patil”)
Regarding Claim 13, the combination of Xiao, Harkema, Naor and Carlton renders obvious the entirety of Claim 11 as explained above.
The combination of Xiao, Harkema, Naor and Carlton does not disclose:
wherein the controller is configured to: under the first patient state, predict, using a trained machine-learning model and without delivering electrostimulation, one or more clinical effects for untested stimulation parameter values or untested electrode configurations in the identified search space;
evaluate a clinical response indicator using the predicted one or more clinical effects;
and determine an estimated base stimulation setting associated with the clinical response indicator evaluated using the predicted one or more clinical effects
Patil describes a “System and method to predict target volume region for therapeutic tissue activation” (Title). Patil is thus analogous art.
Patil discloses:
wherein the controller is configured to: under the first patient state, predict, using a trained machine-learning model and without delivering electrostimulation, one or more clinical effects for untested stimulation parameter values or untested electrode configurations in the identified search space; (Para. [0007], “…one example method for predicting a location within the brain of an individual afflicted with an illness or disorder for stimulation treatment includes: extending a microelectrode along a trajectory within the brain of the individual; receiving, via the microelectrode, electrophysiology data at a plurality of intervals along the trajectory, the electrophysiology data being indicative of neural activity of the individual; and, utilizing, via one or more processors, a machine learning model trained on clinically-determined stimulation treatment of a plurality of similarly-afflicted individuals to predict a tissue activation volume within the brain of the individual based on the electrophysiology data received along the trajectory…”);
evaluate a clinical response indicator using the predicted one or more clinical effects; (Para. [0007], “…analyzing the predicted tissue activation volumes based on a stimulation treatment criteria to determine a tissue activation volume for stimulation treatment….”);
and determine an estimated base stimulation setting associated with the clinical response indicator evaluated using the predicted one or more clinical effects (Para. [0007], “…selecting one of the plurality of trajectories associated with the determined tissue activation volume for treatment of the individual.”).
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of combined Xiao, Harkema, Naor and Carlton with the teachings of Patil (i.e., to use a trained machine learning model to predict the clinical effect of a potential stimulation prior to applying it, and use the prediction to determine stimulation parameters in the manner taught by Patil) in order to “improve the efficiency of therapeutic tissue stimulation for an individual and to more accurately predict a three-dimensional span for therapeutic stimulation” because “[t]he effectiveness of the treatment DBS treatment relies on a time-consuming empirical examination by medical personnel” (Patil at Para. [0003]).
Claims 15-18 and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over previously cited US 2020/0129757 A1 to Xiao (“Xiao”) in view of WO 2020/206387 A1 to Harkema et al. (“Harkema”),previously cited US 2009/0287273 A1 to Carlton et al. (“Carlton”) and US 20210339024 A1 to Naor et al. (“Naor”).
Regarding Independent Claim 15, Xiao discloses:
A method for controlling an implantable stimulator to provide electrostimulation to a neural target of a patient via a lead comprising a plurality of electrodes, the method comprising: (Abstract, “Techniques are disclosed to automate determination of therapy parameter values for adaptive deep brain stimulation (aDBS);” Para. [0021], “Example therapy system 100 includes medical device programmer 104, implantable medical device (IMD) 106, lead extension 110, and leads 114A and 114B with respective sets of electrodes 116, 118. In the example shown in FIG. 1, electrodes 116, 118 of leads 114A, 114B are positioned to deliver electrical stimulation to a tissue site within brain 120….”);
via a programming device: determining a search space of electrode configurations and parameter values for the lead with respect to the neural target …, the search space including a subset of the plurality of electrodes for delivering stimulation and stimulation parameter values or value ranges associated with the subset of electrodes; (Para. [0044], “IMD 106 or programmer 104 (e.g., a medical device), alone or in combination, may automatically determine electrode configuration and therapy parameters. For example, the medical device may determine which electrodes to use for stimulation based on which electrodes are most proximal to the LFP source. As described in more detail, the medical device may also titrate the amplitude or another parameter of the stimulation to automatically determine the stimulation amplitude.”);
Xiao’s “determin[ing] which electrodes to use for stimulation based on which electrodes are most proximal to the LFP source” is such “determining a search space of electrode configurations” as claimed when the term is afforded its broadest reasonable interpretation.
Xiao’s “titrat[ing] the amplitude or another parameter of the stimulation to automatically determine the stimulation amplitude” is such “determining a search space of … parameter values for the lead with respect to the neural target” as claimed when the term is afforded its broadest reasonable interpretation.
evaluating a clinical response indicator responsive to electrostimulation delivered using electrodes and stimulation parameter values within the determined search space under a first patient state; (Para. [0056], “…in response to delivery of a present electrical stimulation (e.g., using electrodes 116, 118 selected based on the CSD values) having a present therapy parameter value, IMD 106 may determine a present power value of power in a frequency band (e.g., beta band) in the bioelectric signal generated by the LFP source and sensed by sense electrodes. … if the difference between the present power value and the previous power value is less than a threshold value (e.g., 0.5 uV/√{square root over (Hz)} as one non-limiting example), further adjustment of the therapy value may not provide noticeably more effective therapy.”);
Xiao’s “present” state (i.e., “a present electrical stimulation,” “a present therapy parameter value,” etc.) is such a “first patient state” as claimed when the term is afforded its broadest reasonable interpretation.
Xiao’s use of “the difference between the present power value and the previous power value” to determine whether “further adjustment of the therapy value” will “provide noticeably more effective therapy” is such “evaluat[ing] a clinical response indicator responsive to electrostimulation delivered using electrodes and stimulation parameter values within the identified search space” when the term is afforded its broadest reasonable interpretation.
Xiao’s “determin[ing] a present power value of power in a frequency band” is such “determin[ing] at least one base stimulation setting corresponding to the clinical response indicator satisfying a specific condition” as claimed when the term is afforded its broadest reasonable interpretation.
Xiao’s “base stimulation setting” includes “an optimal electrode configuration and an optimal stimulation parameter value” because:
Xiao’s “present power value” is based on Xiao’s CSD values (see, e.g., Xiao at Para. [0083] elaborating on CSD values, “To determine which electrodes 116, 118 to use for delivering electrical stimulation, processing circuitry 210 may determine which electrodes 116, 118 have the greatest current source density (CSD) value due to sensing of the LFP signal from the LFP source.”), and thus includes “an optimal electrode configuration;” and
Xiao’s “present power value” is based on Xiao’s “present therapy parameter value” (see, e.g., Xiao at Para. [0015] elaborating on therapy parameter values, “This disclosure describes example techniques to automatically determine values of electrical stimulation therapy parameters, such as electrical stimulation amplitude values…;” see also Xiao at Para. [0065], “An example range of electrical stimulation parameters believed to be effective in DBS to manage a movement disorder of patient include…”), and thus includes “an optimal stimulation parameter value.”
determining at least one base stimulation setting corresponding to the clinical response indicator satisfying a specific condition, the at least one base stimulation setting including an optimal electrode configuration and an optimal stimulation parameter value; (Para. [0056], “…in response to delivery of a present electrical stimulation (e.g., using electrodes 116, 118 selected based on the CSD values) having a present therapy parameter value, IMD 106 may determine a present power value of power in a frequency band (e.g., beta band) in the bioelectric signal generated by the LFP source and sensed by sense electrodes. … if the difference between the present power value and the previous power value is less than a threshold value (e.g., 0.5 uV/√{square root over (Hz)} as one non-limiting example), further adjustment of the therapy value may not provide noticeably more effective therapy.”).
Xiao’s “determin[ing] a present power value of power in a frequency band” is such “determin[ing] at least one base stimulation setting corresponding to the clinical response indicator satisfying a specific condition” as claimed when the term is afforded its broadest reasonable interpretation.
Xiao’s “base stimulation setting” includes “an optimal electrode configuration and an optimal stimulation parameter value” because:
Xiao’s “present power value” is based on Xiao’s CSD values (see, e.g., Xiao at Para. [0083] elaborating on CSD values, “To determine which electrodes 116, 118 to use for delivering electrical stimulation, processing circuitry 210 may determine which electrodes 116, 118 have the greatest current source density (CSD) value due to sensing of the LFP signal from the LFP source.”), and thus includes “an optimal electrode configuration;” and
Xiao’s “present power value” is based on Xiao’s “present therapy parameter value” (see, e.g., Xiao at Para. [0015] elaborating on therapy parameter values, “This disclosure describes example techniques to automatically determine values of electrical stimulation therapy parameters, such as electrical stimulation amplitude values…;” see also Xiao at Para. [0065], “An example range of electrical stimulation parameters believed to be effective in DBS to manage a movement disorder of patient include…”), and thus includes “an optimal stimulation parameter value.”
and storing in a memory the determined search space and the at least one base stimulation setting associated with the corresponding clinical response indicator (Para. [0062], “…memory 211 stores therapy programs 214, previous power value 216, and sense electrode combinations and associated stimulation electrode combinations 218, in separate memories within memory 211 or separate areas within memory 211. Each stored therapy program 214 defines a particular set of electrical stimulation parameters (e.g., a therapy parameter set), such as a stimulation electrode combination, electrode polarity, current or voltage amplitude, pulse width, and pulse rate.”).
and, via a therapy titration user interface device…: under a second patient state different from the first patient state, evaluating the clinical response indicator responsive to electrostimulation in accordance with the at least one base stimulation setting; (Para. [0017], “The IMD or programmer may titrate one or more of the therapy parameters using various example techniques. As one example, the amplitude of the stimulation therapy is gradually adjusted (e.g., increased) until a difference in a current beta band signal power a previous beta band signal power, e.g., obtained from local field potential (LFP) signals, is less than a predetermined threshold difference value, or until the patient experiences undesirable side effects.”);
modifying the at least one base stimulation setting by iteratively adjusting the optimal electrode configuration or the optimal stimulation parameter value within the search space previously determined by the programming device and stored in the memory, until the modified clinical response indicator satisfies a specific condition under the second patient state; (Para. [0058], “… if the difference is greater than a threshold value, the medical device may iteratively adjust the present therapy parameter value and deliver electrical stimulation with the adjusted parameter value until the difference between the present power value (e.g., power value of the power in the frequency band in the current iteration) and the previous power value (e.g., power value of the power in the frequency band in the previous iteration) is less than the threshold value. Once the difference becomes less than the threshold value, the medical device may cease adjustment of the present therapy parameter value and set a final therapy parameter value equal to the present therapy parameter value.”);
storing in the memory the modified at least one base stimulation setting associated with the modified clinical response indicator; (Para. [0079], “The updates to the therapy programs may be stored within therapy programs 214 portion of memory 211.”);
and generating a control signal to the implantable stimulator and causing delivery of electrostimulation to the neural target in accordance with the modified at least one base stimulation setting. (Para. [0058], “The medical device may cause delivery of electrical stimulation having the final therapy parameter value.”).
Xiao does not disclose:
based on at least one of (i) spatial information of the lead or (ii) physiological information sensed by the plurality of electrodes,
a therapy titration user interface device, different and separate from the programming device and communicatively coupled to the implantable stimulator
That is, Xiao’s “therapy titration user interface device” is not “different and separate from the programming device and communicatively coupled to the implantable stimulator”
based on a comparison between the clinical response indicator under the second patient state and the clinical response indicator under the first patient state, identifying one or more clinical effects that have worsened from the first patient state to the second patient state, and modifying the clinical response indicator by increasing respective weight factors for the identified one or more clinical effects;
Harkema describes a “closed loop system for control of spinal cord epidural stimulation” (Abstract). Harkema is analogous art.
Harkema discloses:
a therapy titration user interface device, different and separate from the programming device and communicatively coupled to the implantable stimulator (Paras. [0014] and [0015]; Fig. 1, “second controller 16;” “Line A,” “Line B,” Line C” and “Line D” show such “communicative coupling” as claimed).
This limitation is being interpreted similarly to the similar Claim 1 limitation, as explained above.
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Xiao with the teachings of Harkema (i.e., to modify the device of Xiao such that Xiao’s “therapy titration user interface device” is different and separate from Xiao’s programming device and communicatively coupled to Xiao’s implantable stimulator in the manner of Harkema’s “second controller 16” and “first controller 14”) in order to “generate complex multi-system stimulation patterns in real-time … for improving regulation and function” (Harkema at Para. [0003]).
Carlton describes “A therapy tracking system and method [which includes] a processor that obtains physiological information regarding a patient and a time period during which a deep brain stimulation (DBS) therapy is conducted.” Carlton is analogous art.
Carlton discloses:
based on a comparison between the clinical response indicator under the second patient state and the clinical response indicator under the first patient state, identifying one or more clinical effects that have worsened from the first patient state to the second patient state, (Para. [0221], “FIG. 3 j illustrates generally an example of displaying prior stimulation areas in two or three dimensions as well as indicating (e.g., labeled via color, texture, size, etc.) those stimulation areas that have been associated with one or more side effects. In the example of FIG. 3 j, the side effect areas are displayed in yellow outside of the currently represented VOA. … This may be helpful to the user by indicating those areas which may be stimulated without causing a side effect. A user may thereby determine areas in which to avoid stimulation;” Para. [0224], “In an example, for any one or more of the molds, the side effects can be distinguished as having varying levels of effect or severity. In other examples, one or more structures can be identified in relation to a benefit or side effect, in conjunction with, or instead of its anatomical name. In an example, the label (e.g., a color, a shade, etc.) of a structure can be affected by a degree or severity of the benefit or side effect. In an example, the greater the benefit or the worse the side effect, the darker or lighter the color or shading;” Para. [0314], “A clinician may subsequently test the system-suggested parameters or similar parameters, and adjust the parameters using some of the methods described above, since the resulting benefits and side effects may be different than those anticipated by the system.”);
and modifying the clinical response indicator by increasing respective weight factors for the identified one or more clinical effects; (Paras. [0349] through [0357], “8. based on the noted benefits and side effects relative to the various tested VOAs, the system determines and displays: a. a new target stimulation volume for each benefit individually; b. a collective target stimulation volume that incorporates an addition of all the volumes of step 8(a); c. side effect volumes for each individual side effect; and/or d. a collective side effect volume that incorporates the addition of all side effects volumes of step 8(c); 9. the system estimates and outputs: a. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a specific benefit; and b. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a collective therapy where: i. for example in Parkinson's, a particular benefit such as tremor may be weighted differently than rigidity, the goal of the stimulation settings being to optimize the total benefit to the patient;…”).
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of combined Xiao and Harkema with the teachings of Carlton (i.e., to refine Xiao’s “clinical response indicator” such that it incorporates Carlton’s identification of one or more clinical effects that have worsened and subsequent parameter modification of a clinical response indicator by increasing respective weight factors for the identified clinical effects) in order “to tailor the DBS parameters (such as which one or more of the stimulating electrode contacts to use, the stimulation pulse amplitude, the stimulation pulse width, and/or the stimulation frequency) for a particular patient to improve the effectiveness of the DBS therapy” (Carlton at Para. [0012]).
Naor describes “A method for selecting stimulation treatment parameter values…” (Abstract). Naor is analogous art.
Naor teaches:
based on at least one of (i) spatial information of the lead or (ii) physiological information sensed by the plurality of electrodes, (Abstract, “A method for selecting stimulation treatment parameter values, including: receiving signals related to a patient condition from at least one sensor, during and/or following at least one brain stimulation session, in which stimulation is delivered in at least one location within the brain, using at least one set of treatment parameter values; analyzing the received signals to quantitatively assess at least one treatment side effect and at least one symptomatic effect; selecting a set of treatment parameter values based on the quantitative assessment of the treatment side effects and the symptomatic effect.”).
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of combined Xiao, Carlton and Harkema with the teachings of Naor (i.e., to use such physiological information sensed by the plurality of electrodes as the basis of Xaio’s search space determination) in order to facilitate treatment that aligns with symptom level, change in symptom level, side effect level and change in side effect level (Naor at Para. [0133]).
Regarding Claim 17, the combination of Xiao, Harkema and Carlton renders obvious the entirety of Claim 15 as explained above.
Carlton additionally discloses:
comprising: displaying graphically, on a user interface of the therapy titration user interface device, a heatmap of the determined search space depicting intensities of clinical responses to electrostimulation over a range of electrode positions on the lead and a range of stimulation parameter values; (Para. [0202], “…the system is configured to identify overlapping beneficial and/or adverse regions in a similar manner. For example, the system may store information regarding one or more benefits or side effects with respect to structures in an atlas or map, such that when those structures are stimulated, the stimulation may cause certain therapeutic benefits and/or side effects. This benefit/side effect atlas or map can be stored and shown in two or three dimensions. In certain examples, different benefits or side effects can be identified by a display using different color coded structures or substructures, different intensity patterns, different hatching patterns, via text on screen, etc., as shown in FIGS. 3 e-3 f, in which overlapping areas between a VOA and an anatomical structure or substructure are highlighted in different ways.”).
Xiao additionally discloses:
and receiving user input to modify the at least one base stimulation setting (Para. [0111], “User interface 302 may include a button or keypad, lights, a speaker for voice commands, a display, such as a liquid crystal (LCD), light-emitting diode (LED), or organic light-emitting diode (OLED). In some examples the display may be a touch screen. User interface 302 may be configured to display any information related to the delivery of stimulation therapy, identified patient behaviors, sensed patient parameter values, patient behavior criteria, or any other such information. User interface 302 may also receive user input via user interface 302. The input may be, for example, in the form of pressing a button on a keypad or selecting an icon from a touch screen;” Para. [0041], “Programmer 104 may also provide an indication to patient 112 when therapy is being delivered, when patient input has triggered a change in therapy or when the power source within programmer 104 or IMD 106 needs to be replaced or recharged. For example, programmer 104 may include an alert LED, may flash a message to patient 112 via a programmer display, generate an audible sound or somatosensory cue to confirm patient input was received, e.g., to indicate a patient state or to manually modify a therapy parameter.”).
Regarding Claim 18, the combination of Xiao, Harkema, Carlton and Naor renders obvious the entirety of Claim 15 as explained above.
Xiao additionally discloses:
comprising determining, and storing in the memory, a plurality of base stimulation settings each associated with respective clinical response indicators, … the plurality of base stimulation settings each including respective optimal electrode configurations and respective optimal stimulation parameter values (Para. [0062], “In the example shown in FIG. 2, memory 211 stores therapy programs 214, previous power value 216, and sense electrode combinations and associated stimulation electrode combinations 218, in separate memories within memory 211 or separate areas within memory 211. Each stored therapy program 214 defines a particular set of electrical stimulation parameters (e.g., a therapy parameter set), such as a stimulation electrode combination, electrode polarity, current or voltage amplitude, pulse width, and pulse rate.”);
Xiao’s above-indicated items are “each associated with” Xiao’s clinical response indicators.
Carlton additionally discloses:
the respective clinical response indicators each evaluated under the first patient state using one or more clinical effects weighted by respective weight factors, (Para. [0221], “FIG. 3 j illustrates generally an example of displaying prior stimulation areas in two or three dimensions as well as indicating (e.g., labeled via color, texture, size, etc.) those stimulation areas that have been associated with one or more side effects. In the example of FIG. 3 j, the side effect areas are displayed in yellow outside of the currently represented VOA. … This may be helpful to the user by indicating those areas which may be stimulated without causing a side effect. A user may thereby determine areas in which to avoid stimulation;” Para. [0224], “In an example, for any one or more of the molds, the side effects can be distinguished as having varying levels of effect or severity. In other examples, one or more structures can be identified in relation to a benefit or side effect, in conjunction with, or instead of its anatomical name. In an example, the label (e.g., a color, a shade, etc.) of a structure can be affected by a degree or severity of the benefit or side effect. In an example, the greater the benefit or the worse the side effect, the darker or lighter the color or shading;” Para. [0314], “A clinician may subsequently test the system-suggested parameters or similar parameters, and adjust the parameters using some of the methods described above, since the resulting benefits and side effects may be different than those anticipated by the system;” Paras. [0349] through [0357], “8. based on the noted benefits and side effects relative to the various tested VOAs, the system determines and displays: a. a new target stimulation volume for each benefit individually; b. a collective target stimulation volume that incorporates an addition of all the volumes of step 8(a); c. side effect volumes for each individual side effect; and/or d. a collective side effect volume that incorporates the addition of all side effects volumes of step 8(c); 9. the system estimates and outputs: a. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a specific benefit; and b. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a collective therapy where: i. for example in Parkinson's, a particular benefit such as tremor may be weighted differently than rigidity, the goal of the stimulation settings being to optimize the total benefit to the patient;…”).
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method of combined Xiao, Harkema and Carlton with the teachings of Carlton (i.e., to refine Xiao’s “clinical response indicator” such that it incorporates Carlton’s weighting of clinical effects by respective weight factors for the identified clinical effects) in order “to tailor the DBS parameters (such as which one or more of the stimulating electrode contacts to use, the stimulation pulse amplitude, the stimulation pulse width, and/or the stimulation frequency) for a particular patient to improve the effectiveness of the DBS therapy” (Carlton at Para. [0012]).
Regarding Claim 20, the combination of Xiao, Harkema, Carlton and Naor renders obvious the entirety of Claim 18 as explained above.
Xiao additionally discloses:
via the therapy titration user interface device: under a second patient state different from the first patient state, evaluating the clinical response indicators responsive to electrostimulation in accordance with the plurality of base stimulation settings; (Para. [0017], “The IMD or programmer may titrate one or more of the therapy parameters using various example techniques. As one example, the amplitude of the stimulation therapy is gradually adjusted (e.g., increased) until a difference in a current beta band signal power a previous beta band signal power, e.g., obtained from local field potential (LFP) signals, is less than a predetermined threshold difference value, or until the patient experiences undesirable side effects.”);
based on a comparison between the clinical response indicators under the second patient state and the clinical response indicators under the first patient state, selecting a base stimulation setting from the plurality of base stimulation settings; (Para. [0063], “Previous power value 216 is indicative of a power level of power in a frequency band of a bioelectric signal generated in response to delivery of a previous electrical stimulation having a previous therapy parameter value different than the present therapy parameter value. As described in more detail, in some examples, IMD 106 may determine a difference between previous power value 216 and the present power value to determine whether further adjustment to a therapy parameter value is needed as a way to automatically titrate to the therapy parameter to an appropriate value.”);
modifying the selected base stimulation setting by iteratively adjusting an optimal electrode configuration or an optimal stimulation parameter value of selected base stimulation setting within the determined search space, until the clinical response indicator associated with the selected base stimulation setting satisfies a specific condition under the second patient state; (Para. [0058], “… if the difference is greater than a threshold value, the medical device may iteratively adjust the present therapy parameter value and deliver electrical stimulation with the adjusted parameter value until the difference between the present power value (e.g., power value of the power in the frequency band in the current iteration) and the previous power value (e.g., power value of the power in the frequency band in the previous iteration) is less than the threshold value. Once the difference becomes less than the threshold value, the medical device may cease adjustment of the present therapy parameter value and set a final therapy parameter value equal to the present therapy parameter value.”);
storing in the memory the modified selected base stimulation setting; (Para. [0079], “The updates to the therapy programs may be stored within therapy programs 214 portion of memory 211.”);
and generate a control signal to the implantable stimulator to deliver electrostimulation in accordance with the modified selected base stimulation setting (Para. [0058], “The medical device may cause delivery of electrical stimulation having the final therapy parameter value.”).
Regarding Claim 21, the combination of Xiao, Harkema, Carlton and Naor renders obvious the entirety of Claim 15 as explained above.
Carlton additionally discloses:
wherein the one or more clinical effects include one or more motor symptoms including bradykinesia, tremor, or rigidity (Paras. [0349] through [0357], “8. based on the noted benefits and side effects relative to the various tested VOAs, the system determines and displays: a. a new target stimulation volume for each benefit individually; b. a collective target stimulation volume that incorporates an addition of all the volumes of step 8(a); c. side effect volumes for each individual side effect; and/or d. a collective side effect volume that incorporates the addition of all side effects volumes of step 8(c); 9. the system estimates and outputs: a. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a specific benefit; and b. stimulation settings that result in a VOA that fills the intended benefit volumes without filling the side effect volumes for a collective therapy where: i. for example in Parkinson's, a particular benefit such as tremor may be weighted differently than rigidity, the goal of the stimulation settings being to optimize the total benefit to the patient;…”)
Regarding Claim 22, the combination of Xiao, Harkema, Carlton and Naor renders obvious the entirety of Claim 15 as explained above.
Carlton additionally discloses:
comprising, via the therapy titration user interface device, receiving information about the one or more clinical effects via a user interface of the therapy titration user interface device or via one or more sensors communicatively coupled to the therapy titration user interface device (Para. [0021], “The at least one of the side effect and the benefit may be received as user input via a user interface of the system. For example, the physician may observe and enter into the system certain benefits and/or side effects resulting from a stimulation using a certain set of stimulation parameters.”).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over previously cited US 2020/0129757 A1 to Xiao (“Xiao”) in view of WO 2020/206387 A1 to Harkema et al. (“Harkema”), previously cited US 2009/0287273 A1 to Carlton et al. (“Carlton”) US 20210339024 A1 to Naor et al. (“Naor”) as applied to Claim 18 above, and further in view of previously cited US 2021/0085257 A1 to Patil et al. (“Patil”)
Regarding Claim 19, the combination of Xiao, Harkema, Carlton and Naor renders obvious the entirety of Claim 18 as explained above.
The combination of Xiao, Harkema, Carlton and Naor does not disclose:
under the first patient state, predicting, using a trained machine-learning model and without delivering electrostimulation, one or more clinical effects for untested stimulation parameter values or untested electrode configurations in the determined search space;
evaluating a clinical response indicator using the predicted one or more clinical effects;
and determining an estimated base stimulation setting associated with the clinical response indicator evaluated using the predicted one or more clinical effects.
Patil describes a “System and method to predict target volume region for therapeutic tissue activation” (Title). Patil is thus analogous art.
Patil discloses:
under the first patient state, predicting, using a trained machine-learning model and without delivering electrostimulation, one or more clinical effects for untested stimulation parameter values or untested electrode configurations in the identified search space; (Para. [0007], “…one example method for predicting a location within the brain of an individual afflicted with an illness or disorder for stimulation treatment includes: extending a microelectrode along a trajectory within the brain of the individual; receiving, via the microelectrode, electrophysiology data at a plurality of intervals along the trajectory, the electrophysiology data being indicative of neural activity of the individual; and, utilizing, via one or more processors, a machine learning model trained on clinically-determined stimulation treatment of a plurality of similarly-afflicted individuals to predict a tissue activation volume within the brain of the individual based on the electrophysiology data received along the trajectory…”);
evaluating a clinical response indicator using the predicted one or more clinical effects; (Para. [0007], “…analyzing the predicted tissue activation volumes based on a stimulation treatment criteria to determine a tissue activation volume for stimulation treatment….”);
and determining an estimated base stimulation setting associated with the clinical response indicator evaluated using the predicted one or more clinical effects. (Para. [0007], “…selecting one of the plurality of trajectories associated with the determined tissue activation volume for treatment of the individual.”).
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of combined Xiao, Harkema, Carlton and Naor with the teachings of Patil (i.e., to use a trained machine learning model to predict the clinical effect of a potential stimulation prior to applying it, and use the prediction to determine stimulation parameters in the manner taught by Patil) in order to “improve the efficiency of therapeutic tissue stimulation for an individual and to more accurately predict a three-dimensional span for therapeutic stimulation” because “[t]he effectiveness of the treatment DBS treatment relies on a time-consuming empirical examination by medical personnel” (Patil at Para. [0003]).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/C.J.M./Examiner, Art Unit 3796
/Jennifer Pitrak McDonald/Supervisory Patent Examiner, Art Unit 3796
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