DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 7, 17-18, 20 and 22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 7 is rejected because the specification fails to disclose the claimed ultrasound regimen of at least three ultrasound cycles lasting for at least a minute and separated by an adjustable off period of at least 4 hours repeated daily for 15 days as now claimed. Examiner respectfully notes that while Fig. 46 and Paragraphs [0206] of the PG Pub discloses three, 1 minute cycles continued for at least 15 days, such a protocol does not specify that each cycle is separated by at least 4 hours.
Claim Rejections - 35 USC § 103
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 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) 1-2, 7-8, 20, 23-25 and 27-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 2013/0178910 to Azamian et al. “Azamian” in view of U.S. Publication No. 2010/0028968 to Rubin et al. “Rubin” and U.S. Publication No. 2017/0246481 to Mishelevich.
With respect to Claims 1-2, 7-8 and 20, Azamian discloses a system and method to treat a subject having diabetes or symptoms associated with diabetes by ultrasonic modulation (Abstract; Paragraph [0079]). Azamian explains that “targeted neuromodulation” of liver nerve fibers can be used for the treatment of any combination of diabetes including insulin resistance (Paragraphs [0007] and [0245]). Examiner notes that improving insulin resistance would reduce the concentration of insulin within the body in its broadest reasonable interpretation. Examiner also notes that the area including hepatic veins, hepatic arteries and/or the hepatic plexus would be considered the porta hepatis in its broadest reasonable interpretation. Azamian discloses where the treatment can be pulsed or continuous and treatment time durations can range from 1 second to 1 hour, greater than 1 hour, 5 seconds to 30 minutes, etc. (Paragraphs [0173]-[0174], [0209]).
While Azamian discloses where the treatment can be pulsed or continuous and treatment time durations can range from 1 second to 1 hour, greater than 1 hour, 5 seconds to 30 minutes, etc. (Paragraphs [0173]-[0174], [0209]), Azamian does not disclose the specific dose regime as now claimed (e.g. at least 3 ultrasound cycles for at least one minute repeated for at least 15 days). Examiner also notes that in order to specifically target the hepatic arteries, veins, or nerves and treat them according to the disclosed pattern and timing parameters described above, Azamian’s modulation system would include a controller in its broadest reasonable interpretation.
Rubin teaches from within a similar field of endeavor with respect to ultrasound treatment systems and methods to improve insulin resistance (Paragraph [0041]) where treatment may be administered periodically (e.g. every 4 hours) where treatment may stop and resume at various points in the day (Paragraph [0007]).
In addition, Mishelevich teaches from within a similar field of endeavor with respect to non-invasive ultrasound modulation systems and methods (Abstract) where dose regimens are delivered by controlling the direction of energy emission, intensity, frequency, pulse duration, pulse pattern, and phase/intensity relationships for periodic sessions over extended time such as, for example, 30-60 minutes repeated daily for 4-6 weeks (Paragraphs [0175]-[0176]). In one embodiment, Mishelevich discloses a burst mode pattern where instead of having a constant stream of pulses, the ultrasound modulation is turned on for a period of time and then turned off and repeated after a period of time. Each of the on and off interval times may be selected from 1 second ranging up to 500 seconds (Paragraph [0159]). Such a pattern is considered to read on the claimed limitation of at least three ultrasound cycles wherein each cycle lasts for at least one minute and is applied at separate time points in its broadest reasonable interpretation. Mishelevich explains anatomical targets may be “up regulated” or “down regulated” based on coordinated control of the direction of energy emission, intensity, session duration, frequency and number of targets via a controller (Paragraphs [0051]-[0052], [0061], [0094], [0638] and 500 in Fig. 5 and corresponding descriptions) and the system may use ancillary monitoring or imaging to provide feedback (Paragraphs [0052], [0142] and 520 in Fig. 5 and corresponding descriptions).
Accordingly, one skilled in the art would have been motivated to have modified the pulsed treatment described by Azamian to be controlled and targeted cycles of ultrasound repeated daily over 4-6 weeks as described by Rubin and Mishelevich in order to enhance the efficacy of the treatment and create a prolonged treatment effect on the patient. Such a modification merely involves combining prior art elements according to known techniques to yield predictable results (MPEP 2143). Applicant’s specification explains that targeting the porta hepatis with an ultrasound dose regimen modulates blood glucose concentration (Paragraph [0194]) and also changes hypothalamic concentrations of NPY and NE at a distal site not directly subjected to stimulation, further inducing increased phosphorylation oof ion channels indicative of increased activity of the insulin signaling pathway, which may indicate improved insulin sensitivity as well as improved glucose utilization (Paragraphs [0195]-[0196]). Thus, the modified ultrasound dose regimen described above to the porta hepatis of the liver would necessarily cause a change in concentration of one or more molecules at a hypothalamic site that is distal from the liver, wherein the change in concentration of the one or more molecules corresponds to a systemic improvement in insulin sensitivity in its broadest reasonable interpretation.
Regarding Claim 23, Azamian makes it clear that the modulation means may target the nerve fibers in a minimally invasive surgical delivery of the modulation means (e.g. energy application device), in an open surgical procedure or as part of a non-invasive procedure (Paragraphs [0014]-[0017], [0021] and [0227]).
AS for Claims 24-25 and 27-28, Examiner notes that such claim limitations do not add any structural components to the system and appear to be the result of applying ultrasound energy to the port hepatis as described above. Accordingly, the system disclosed above would read on the functional language claimed.
Claim(s) 3 and 11-15 and 17-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Azamian, Rubin and Mishelevich as applied to claims 1 and 7-8 above, and further in view of EP 2821103 to Tyler.
As for Claims 3, 11-15 and 17-18, Azamian, Rubin and Mishelevich discloses a modulation system as described above. However, Azamian, Rubin and Mishelevich does not expressly disclose an assessment device configured to provide input indicative of the circulating concentration of insulin.
Tyler teaches from within a similar field of endeavor with respect to modulation systems and methods comprising an energy application device (e.g., ultrasound system comprising a transducer) (Paragraphs [0009] and [0016]) configured to apply energy to a region of interest (e.g., target) in a subject where a blood glucose monitoring device may be used to provide feedback for the ultrasound treatment (Paragraph [0089]). For example, Tyler explains that the feedback information would be provided to the ultrasound device in order to alter or maintain the treatment. Given the known physiological connection between glucose and insulin (Azamian; Paragraphs [0003]-[0005]), Examiner notes such information would be indicative of a general circulating concentration of insulin in its broadest reasonable interpretation.
Accordingly, one skilled in the art would have been motivated to have modified the modulation system and method described by Azamian and Mishelevich to include a treatment feedback means described by Tyler in order to selectively apply and/or adjust the energy application accordingly to a desired portion of the liver as such a modification merely involves combining prior art elements according to known techniques to yield predictable results (MPEP 2143).
Claim(s) 3 is/are alternatively rejected under 35 U.S.C. 103 as being unpatentable Azamian, Rubin and Mishelevich as applied to claim 1 above, and further in view of U.S. Publication No. 2007/0162085 to DiLorenzo.
As for Claim 3, Azamian, Rubin and Mishelevich discloses a modulation system as described above. However, Azamian, Rubin and Mishelevich does not expressly disclose an assessment device configured to provide input indicative of the circulating concentration of insulin.
DiLorenzo teaches from within a similar field of endeavor with respect to physiological modulation devices and methods (Abstract) where the system includes a sensor array configured to monitor at least one parameter related to glucose, glycogen and insulin level and metabolism (Paragraph [0255]).
Accordingly, one skilled in the art would have been motivated to have modified the modulation system and method described by Azamian, Rubin and Mishelevich to include a treatment feedback means described by DiLorenzo in order to selectively apply and/or adjust the energy application as such a modification merely involves combining prior art elements according to known techniques to yield predictable results (MPEP 2143).
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Azamian, Rubin and Mishelevich as applied to claim 7 above, and further in view of U.S. Publication No. 2018/0042535 to Hezi-Yamit et al. “Hezi-Yamit”.
With respect to Claim 22, Azamian, Rubin and Mishelevich disclose modulation system and method as described above including a feedback loop used to control modulation parameters. However, the art of record does not expressly disclose using a concentration of one or more hypothalamic markers as claimed.
Hezi-Yamit teaches from within a similar field of endeavor with respect to modulation systems and methods where biomarkers, including for example, norepinephrine is/are used as feedback for monitoring neuromodulation efficacy (Abstract; claims 32 and 49). Hezi-Yamit also discloses wherein the system and method may utilize protein target biomarkers including, for example, neurotrophins (Paragraph [0073]) and brain derived neurotrophic factor (BDNF) (Paragraph [0096]). Such biomarkers would be considered hypothalamic markers in its broadest reasonable interpretation in light of Applicant’s specification.
Accordingly, one skilled in the art would have been motivated to use other conventional neuromodulation feedback techniques as described by Hezi-Yamit in order to enhance the efficacy of the treatment and increase patient safety. Such a modification merely involves combining prior art elements according to known techniques to yield predictable results (MPEP 2143).
Claim(s) 7, 17-18 and 20 is/are alternatively rejected under 35 U.S.C. 103 as being unpatentable over Azamian, Rubin, Mishelevich and Tyler.
As for Claim 7 and 20, Azamian discloses a system and method to treat a subject having diabetes or symptoms associated with diabetes by modulation (Abstract; Paragraph [0079]). Azamian explains that “targeted neuromodulation” of liver nerve fibers can treat or reduce the risk of occurrence of symptoms associated with diabetes by decreasing glucose production and/or increasing hepatic glucose uptake (Paragraph [0006]-[0008]). Azamian discloses where the treatment can be pulsed or continuous and treatment time durations can range from 1 second to 1 hour, greater than 1 hour, 5 seconds to 30 minutes, etc. (Paragraphs [0173]-[0174], [0209]). Examiner notes that pulsed treatment sessions that are “greater than 1 hour” would include a time period that is of at least 4 hours in its broadest reasonable interpretation. In addition, off period is determined based on feedback (e.g. timing information) received by the controller.
However, while Azamian discloses where the treatment can be pulsed or continuous and treatment time durations can range from 1 second to 1 hour, greater than 1 hour, 5 seconds to 30 minutes, etc. (Paragraphs [0173]-[0174], [0209]), Azamian does not disclose the specific dose regime as now claimed (e.g. at least 3 ultrasound cycles for at least one minute separated by 4 hours and repeated daily for at least 15 days).
Rubin teaches from within a similar field of endeavor with respect to ultrasound treatment systems and methods to improve insulin resistance (Paragraph [0041]) where treatment may be administered periodically (e.g. every 4 hours) where treatment may stop and resume at various points in the day (Paragraph [0007]).
In addition, Mishelevich teaches from within a similar field of endeavor with respect to non-invasive ultrasound modulation systems and methods (Abstract) where dose regimens are delivered by controlling the direction of energy emission, intensity, frequency, pulse duration, pulse pattern, and phase/intensity relationships for periodic sessions over extended time such as, for example, 30-60 minutes repeated daily for 4-6 weeks (Paragraphs [0175]-[0176]). In one embodiment, Mishelevich discloses a burst mode pattern where instead of having a constant stream of pulses, the ultrasound modulation is turned on for a period of time and then turned off and repeated after a period of time. Each of the on and off interval times may be selected from 1 second ranging up to 500 seconds (Paragraph [0159]). Such a pattern is considered to read on the claimed limitation of at least three ultrasound cycles wherein each cycle lasts for at least one minute and is applied at separate time points in its broadest reasonable interpretation. Mishelevich explains anatomical targets may be “up regulated” or “down regulated” based on coordinated control of the direction of energy emission, intensity, session duration, frequency and number of targets via a controller (Paragraphs [0051]-[0052], [0061], [0094], [0638] and 500 in Fig. 5 and corresponding descriptions) and the system may use ancillary monitoring or imaging to provide feedback (Paragraphs [0052], [0142] and 520 in Fig. 5 and corresponding descriptions).
Accordingly, one skilled in the art would have been motivated to have modified the pulsed treatment described by Azamian to be controlled and targeted cycles of ultrasound repeated daily over 4-6 weeks as described by Rubin and Mishelevich in order to enhance the efficacy of the treatment and create a prolonged treatment effect on the patient. Such a modification merely involves combining prior art elements according to known techniques to yield predictable results (MPEP 2143). Applicant’s specification explains that targeting the porta hepatis with an ultrasound dose regimen modulates blood glucose concentration (Paragraph [0194]) and also changes hypothalamic concentrations of NPY and NE at a distal site not directly subjected to stimulation, further inducing increased phosphorylation oof ion channels indicative of increased activity of the insulin signaling pathway, which may indicate improved insulin sensitivity as well as improved glucose utilization (Paragraphs [0195]-[0196]). Thus, the modified ultrasound dose regimen described above to the porta hepatis of the liver would necessarily cause a change in concentration of one or more molecules at a hypothalamic site that is distal from the liver, wherein the change in concentration of the one or more molecules corresponds to a systemic improvement in insulin sensitivity in its broadest reasonable interpretation.
Further regarding the “feedback”, while Mishelevich provides a feedback means to adjust the modulation, the art of record does not disclose where the assessment device is a glucose monitor.
Tyler teaches from within a similar field of endeavor with respect to modulation systems and methods comprising an energy application device (e.g., ultrasound system comprising a transducer) (Paragraphs [0009] and [0016]) configured to apply energy to a region of interest (e.g., target) in a subject where a blood glucose monitoring device may be used to provide feedback for the ultrasound treatment (Paragraph [0089]). For example, Tyler explains that the feedback information would be provided to the ultrasound device in order to alter or maintain the treatment. Examiner notes that such a feedback loop would read on receiving a pre-treatment glucose concentration and wherein the glucose concentration is lower (e.g., significantly) a result of the treatment in its broadest reasonable interpretation. Furthermore, such information would be indicative of the circulating concentration of insulin in its broadest reasonable interpretation.
Accordingly, one skilled in the art would have been motivated to have modified the modulation system and method described by Azamian, Rubin and Mishelevich to include a treatment feedback means described by Tyler in order to selectively apply and/or adjust the energy application accordingly to a desired portion of the liver as such a modification merely involves combining prior art elements according to known techniques to yield predictable results (MPEP 2143). Moreover, Applicant’s specification explains that targeting the porta hepatis with an ultrasound dose regimen modulates blood glucose concentration (Paragraph [0194]) and also changes hypothalamic concentrations of NPY and NE at a distal site not directly subjected to stimulation, further inducing increased phosphorylation oof ion channels indicative of increased activity of the insulin signaling pathway, which may indicate improved insulin sensitivity as well as improved glucose utilization (Paragraphs [0195]-[0196]). Thus, the modified dose regimen to the porta hepatis of the liver would necessarily cause a change in concentration of one or more molecules at a hypothalamic site that is distal from the liver, wherein the change in concentration of the one or more molecules corresponds to a systemic improvement in insulin sensitivity in its broadest reasonable interpretation.
With respect to Claims 17-18, the modified system and method described by Azamian, Rubin, Mishelevich and Tyler reads on the claimed limitations of using a glucose monitor for feedback in its broadest reasonable interpretation.
Claim(s) 22 is/are alternatively rejected under 35 U.S.C. 103 as being unpatentable over Azamian, Rubin, Mishelevich and Tyler as applied to claim 7 above, and further in view of U.S. Publication No. 2018/0042535 to Hezi-Yamit et al. “Hezi-Yamit”.
With respect to Claim 22, Azamian, Rubin, Mishelevich and Tyler disclose modulation system and method as described above including a feedback loop used to control modulation parameters. However, the art of record does not expressly disclose using a concentration of one or more hypothalamic markers as claimed.
Hezi-Yamit teaches from within a similar field of endeavor with respect to modulation systems and methods where biomarkers, including for example, norepinephrine is/are used as feedback for monitoring neuromodulation efficacy (Abstract; claims 32 and 49). Hezi-Yamit also discloses wherein the system and method may utilize protein target biomarkers including, for example, neurotrophins (Paragraph [0073]) and brain derived neurotrophic factor (BDNF) (Paragraph [0096]). Such biomarkers would be considered hypothalamic markers in its broadest reasonable interpretation in light of Applicant’s specification.
Accordingly, one skilled in the art would have been motivated to use other conventional neuromodulation feedback techniques as described by Hezi-Yamit in order to enhance the efficacy of the treatment and increase patient safety. Such a modification merely involves combining prior art elements according to known techniques to yield predictable results (MPEP 2143).
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-3, 7-8, 11-15, 17-18, 20, 22-25 and 27-28 have been considered but are moot in view of the updated grounds of rejection necessitated by amendment. However, Examiner will address Applicant’s remarks which may still pertain to the current rejection. For example, Applicant argues Azamian fails to disclose reducing the circulating concentration of insulin after repeated application of energy (REMARKS, Pages 7-8) because Azamian specifically discloses increasing insulin secretion in Paragraph [0025]). Examiner respectfully notes Azamian makes it clear that the aforementioned treatment is for all combinations of diabetes including correcting insulin resistance. Examiner notes that correcting or improving insulin resistance would reduce the insulin concentration in the body in its broadest reasonable interpretation. Moreover, Mishelevich explains anatomical targets may be “up regulated” or “down regulated” based on coordinated control of the direction of energy emission, intensity, session duration, frequency and number of targets via a controller (Paragraphs [0051]-[0052], [0061], [0094], [0638] and 500 in Fig. 5 and corresponding descriptions) and the system may use ancillary monitoring or imaging to provide feedback (Paragraphs [0052], [0142] and 520 in Fig. 5 and corresponding descriptions). It is unreasonable for Applicant to only cite one paragraph from the reference and ignore the rest of the disclosure. For reference, Applicant’s specification appears to disclose where the treatment increases circulating insulin (Paragraph [0111]).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER L COOK whose telephone number is (571)270-7373. The examiner can normally be reached M-F approximately 8AM-5PM.
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/CHRISTOPHER L COOK/Primary Examiner, Art Unit 3793
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