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 .
Priority: The current application has the effective filing date of 05/15/2024.
Claim Status
As per applicant’s response received on 06/22/2026, claims 1-21 are pending, and claims 1 and 12 have been amended, and claim 21 has been newly added.
Response to Amendment
Regarding the double patenting rejections, these rejections are maintained. The current claim amendments to claims 1 and 12 are not sufficient to substantially differentiate over the applied parent/copending applications.
As for the outstanding 35 USC 103 rejection based on Levine et al. US 8,788,034 and Simon et al. US 2011/0276112, the Applicant’s arguments have been fully considered but are not persuasive.
In Remarks, pgs. 6-7, the Applicant argued that the applied references alone and in combination fail to teach a method of reversing demyelination as recited in claims 1 and 12. The Applicant argued that Levine contemplates treating inflammation, such as multiple sclerosis which are indicated by different inflammatory markers compared to that of demyelination. As such, the applied references fail to teach biomarkers indicating demyelination. Currently, the amendment “one or more biomarkers indicating demyelination” is not substantially different from the previously limitation “one or more biomarkers for demyelination”, the 103 rejection is maintained. The Examiner respectfully disagrees with the arguments for the following reasons.
Firstly, claim 1 only recites two steps: receiving a command to supply a stimulation based on one or more biomarkers indicating demyelination, and applying electrical stimulation to the patient’s vagus nerve. To claim 1, the argued biomarker step is not a positively recited step. As for claim 12, the claim recites a step for detecting one or more biomarkers, but this step does not explicitly define which biomarkers are detected. Since, the Applicant’s own disclosure (i.e. [0003-0004]) recognizes “multiple sclerosis (MS) is a neurodegenerative disease characterized by demyelination of nerves in the central nervous system”, it is the Examiner’s BRI that biomarkers for MS and demyelination overlap, such as certain biomarkers indicating inflammation.
Secondly, the Applicant has argued that even if there are overlapping biomarkers, the levels of markers would be different compared to that of inflammation or MS. However, these argued types of biomarkers and/or levels are not defined. The detecting step is not even limited by the type of detection or the sensors used. Under BRI, Levine teaches for detecting biomarkers associated with MS and demyelination is sufficient to meet the current claim limitation.
Assuming arguendo, the Applicant’s own disclosure mentions detecting biomarkers indicating demyelination include temperature, cytokine, and sirtuin levels, these are taught Levine: col.9, ll.33-39 and col.10, ll.13-17.
To overcome the current interpretation, the Examiner suggests further streamlining the independent claims with specific biomarkers mentioned in Specification [0063] and/or claim 9 mentions specific biomarkers, and/or the argued levels of said biomarkers indicating demyelination.
The Applicant did not specifically argue claim 11, see Examiner’s rationale above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-6 and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 14 of copending Application No. 19/224,699 (“app’699”). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application recites a method that contains essentially the same steps as recited in the current application, with the exception of intending to treat a different disease. The rejection is as follows:
Claim 1 of the instant application is rejected by claim 1 in app’699 for reciting a method that includes the same steps, i.e. 1) receiving a command to apply a remyelinating stimulation, and 2) applying electrical stimulation between 0.25 mA and 5mA at a duty cycle of less than 10 percent to the patient’s vagus nerve; the only difference is the instant application is for reversing demyelination, and the app’699 is intended for treating multiple sclerosis (MS), but this noted difference pertains to an intended use/functional feature.
Claims 2-6 of the instant application are rejected by claims 2-6 in app’699 for reciting substantially the same claim matter.
Claim 12 of the instant application is rejected by claim 14 in app’699 for reciting that method that includes the same steps, i.e. 1) monitoring for biomarkers of demyelination, 2) receiving a command to apply a remyelinating stimulation, and 3) applying electrical stimulation between about 0.25 mA and about 5mA at a duty cycle of less than 10 percent to the patient’s vagus nerve; the only difference is the instant application is for reversing demyelination, and the app’699 is intended for treating multiple sclerosis.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11 and 18 of U.S. Patent No. 12,172,017 B2 (pat’017). Although the claims at issue are not identical, they are not patentably distinct from each other because Pat’017 discloses a method that contains essentially the same steps as recited in the current application, with the exception of intending to treat a different disease. The rejection is as follows:
Claim 1 of the instant application is rejected by claim 11 in app’699 for reciting a method that includes: controlling and applying electrical stimulation to vagus nerve at a low duty cycle of between 0.25mA to 5mA. Claim 11 does not disclose applying the electrical stimulation at duty cycle of less than 10 percent, but mentions using a low duty cycle, it would have been an obvious to a person of ordinary skill in the art at the time of invention to try at 10 percent duty cycle or less in order to optimize therapeutic results.
Claim 12 of the instant application is rejected by claim 18 in app’699 for reciting a method that includes: receiving biomarker sensor data indicative of demyelination, and controlling and applying electrical stimulation to vagus nerve at a low duty cycle of between 0.25mA to 5mA. Claim 18 does not disclose applying the electrical stimulation at duty cycle of less than 10 percent, but mentions using a low duty cycle, it would have been an obvious to a person of ordinary skill in the art at the time of invention to try at 10 percent duty cycle or less in order to optimize therapeutic results.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 21 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 21, the following limitations are rejected as vague and indefinite: “further comprising inducing remyelination via the duty cycle while allowing an inflammatory response…” The underlined limitation” is an intended results of applying stimulation, but this is not a positive recitation since exactly how this is achieved is not recite; specifically, what are the stimulation parameters used to achieve the recited intended result. Furthermore, the term “allowing” is also confusing as what is performing the ‘allowing.’
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 1-10 and 12-20 and are rejected under 35 U.S.C. 103 as being unpatentable over Levine et al. US 8,788,034 B2 (previously cited) in view of Simon et al. US 2011/0276112 A1 (hereinafter “Simon”).
Note: Levine US 8,788,034 shares a common assignee and a common inventor as the current application, but does not share a common priority chain, this is not a parent application.
Regarding claim 1, Levine discloses a method of reversing demyelination in a patient having a demyelinating disorder (Abstract and col.1, ll.40-52 method and system for treating chronic inflammation and inflammatory disorders using extremely low duty cycles, e.g. col.4, ll.5-14 lists inflammatory disorders with demyelinating symptoms), the method comprising:
receiving, in an implanted vagus nerve stimulator (col.3, ll.39-40 implantable (micro)stimulator), a command (col.3, ll.37-41 controller to set a stimulation dose for the microstimulator; also see col.8, ll.3-6 controller for delivering the stimulation protocol) to apply a remyelinating stimulation to the patient based on one or more biomarkers for demyelination (col.2, ll.5-57 and col.4, ll.15-50 vagus nerve stimulation treatment of a plurality of chronic inflammation diseases, e.g. multiple sclerosis is presented with demyelination; chronic inflammation diseases are monitored via biomarkers , see col.9, ll.31-42).
Levine does not explicitly disclose applying electrical stimulation of between 0.25 mA and 5 mA at a duty cycle of less than 10 percent to the patient's vagus nerve from the implanted vagus nerve stimulator to reverse demyelination and increase remyelination of the patient's nerves. However, Levine discloses applying a stimulation of between 100 µA to 5000 µA, equivalent to 0.1 mA to 5 mA (see Levine: col.5, ll.35-47) for treatment of chronic inflammatory disease intending to reverse demyelination and increase remyelination (see col.9, ll.31-42). Simon, another prior art reference in analogous art in analogous art discloses a method of reversing demyelination in a patient having a demyelinating disorder (see Abstract: electric stimulation is sufficient to encompass the intended use of “reversing demyelination” recited in this claim), the method comprising:
receiving, in a non-invasive vagus nerve stimulator (nerve stimulation device 300), a command to apply a remyelinating stimulation to the patient based on one or more biomarkers for demyelination (see [0048-0049] 300 comprises a control unit 330 for receiving command from a user or based on externally measured parameter, see [0049] “…control of the system may be based upon feedback measured from externally supplied physiological or environmental signals…”); and
applying electrical stimulation of between about 0.25 mA and about 5 mA at a duty cycle of less than 10 percent to the patient’s vagus nerve from the implanted vagus nerve stimulator to reverse demyelination and increase remyelination of the patient’s nerves ([0056:2nd sentence] a VNS therapy, e.g. current between 1 and 2mA, and a duty cycle of 10%, see [0056] and also see [0051, 0053] for adjusting stimulation duty cycle, pulse width/shape/amplitude depending on the type of disease the device is intending to treat etc.).
It would have been obvious to a person of ordinary skill in the art at the time of invention to modify Levine in view of Simon so as to adjust the stimulation to between 1 and 2mA, and a duty cycle of 10%, the motivation for doing so is because Simon explicitly states that this range is typical stimulation waveform parameter values for “invasive vagal nerve stimulation” (Simon: [0056: 1st sentence], Levin teaches invasive vagal nerve stimulation via implantable in col. col.3, ll.37-41).
Regarding claim 2, Levine modified discloses the method of claim 1, and wherein applying comprises applying the electrical stimulation (see rejection to claim 1 above), followed by an off-time of at least 10 minutes. (Levine: col.3, ll.45-50, col.8, ll.21 off time of at least 4 to 48 hrs. Also see claim 11: “A method of treating chronic inflammation in a patient, the method comprising: implanting a microstimulator; and applying only a single supra-threshold stimulus pulse from the microstimulator to the vagus nerve followed by an off-time of at least 4 hours; and reducing a level of inflammation in the patient”, col.10, ll.11-14 stimulation and off time can be increased/decreased to optimize treatment efficacy)
Regarding claim 3, Levine modified discloses the method of claim 1, wherein applying comprises applying the electrical stimulation for less than 2 minutes. (Levine: col.6, ll.6-17 stimulation is delivered is 1 to 5 pulses at one pulse increment, with a pulse width of 20-2000 microseconds, equivalent to .00002 to 0.002 seconds, which would equate to a treatment time of less than 2 minutes in total; also see col.10, ll.11-14 stimulation and off time can be increased/decreased to optimize treatment efficacy)
Regarding claim 4, Levine modified discloses the method of claim 1, wherein applying comprises applying the electrical stimulation for less than 2 minutes, followed by an off-time of at least 10 minutes. (See rejections to claims 2 and 3 above.)
Regarding claim 5, Levine modified discloses the method of claim 1, further comprising continuously monitoring the patient for the one or more biomarkers for demyelination. (Levine: col.9, ll.33-36 monitoring before, during and after treatment of one or more biomarkers for inflammation, including “[f]or example, in treating an inflammatory disorder, a biomarker for inflammation may be monitored, such as a cytokine or other marker...”)
Regarding claim 6, Levine modified discloses the method of claim 1, further comprising detecting the one or more biomarkers for demyelination. (Levine: col.9, ll.33-36 cytokine is a biomarker for demyelination)
Regarding claim 7, Levine modified discloses the method of claim 6, wherein detecting the one or more biomarkers for demyelination comprises monitoring the patient's temperature. (Levine: col.9, ll. 33-39 “For example, in treating an inflammatory disorder, a biomarker for inflammation may be monitored, such as a cytokine or other marker. In some variations, monitoring the patient may include assessing the patient visually (e.g., for swelling, body temperature, etc.)…”)
Regarding claim 8, Levine modified discloses the method of claim 6, wherein detecting the one or more biomarkers for demyelination comprises determining a level of tumor necrosis factor in the patient's blood or cerebrospinal fluid. (Levine: col.10, ll.16-17 sirtuin level)
Regarding claim 9, Levine modified discloses the method of claim 6, wherein the one or more biomarkers for demyelination is selected from the group consisting of neurofilament, glial fibrillary acidic protein, the monocyte macrophage marker CD 163, the glial activation marker YKL-40, the B cell chemoattractant CXCL13, miRNA, mRNA, myelin reactive t cells, Kir4.1 antibodies, osteopontin, and microbiome associated lipopeptides. (Levine: col.10, ll.13-17 TNF and sirtuin levels, cytokine levels)
Regarding claim 10, Levin modified discloses the method of claim 1, further comprising repeatedly applying the duty-cycle electrical stimulation of between 0.25 and 5 mA to the patient's vagus nerve for less than 2 minutes (Levine: col.6, ll.6-17 stimulation is delivered is 1 to 5 pulses at one pulse increment, with a pulse width of 20-2000 microseconds, equivalent to .00002 to 0.002 seconds, which would equate to a treatment time of less than 2 minutes in total), followed by an off-time of between 12 and 48 hours. (Levine: col.3, ll.45-50, col.8, ll.21 off time between about 12 to 48 hours; also see col.10, ll.11-14 stimulation and off time can be increased/decreased to optimize treatment efficacy)
Regarding claim 12, Levine discloses a method of reversing demyelination in a patient having a demyelinating disorder (Abstract and col.1, ll.40-52 method and system for treating chronic inflammation and inflammatory disorders using extremely low duty cycles, e.g. col.4, ll.5-14 lists inflammatory disorders with demyelinating symptoms), the method comprising:
detecting one or more biomarkers for demyelination from the patient (col.9, ll.33-39 detecting cytokine, which is a biomarker for demyelination); and
receiving, in an implanted vagus nerve stimulator (col.3, ll.39-40 implantable (micro)stimulator), a command (col.3, ll.37-41 controller to set a stimulation dose for the microstimulator; also see col.8, ll.3-6 controller for delivering the stimulation protocol) to apply a remyelinating stimulation to the patient based on a level of the detected one or more biomarkers for demyelination (col.2, ll.5-57 and col.4, ll.15-50 vagus nerve stimulation treatment of a plurality of chronic inflammation diseases, e.g. multiple sclerosis is presented with demyelination; chronic inflammation diseases are monitored via biomarkers , see col.9, ll.31-42).
Levine does not explicitly disclose applying electrical stimulation of between 0.25 mA and 5 mA at a duty cycle of less than 10 percent to the patient's vagus nerve from the implanted vagus nerve stimulator to reverse demyelination and increase remyelination of the patient's nerves. However, Levine discloses applying a stimulation of between 100 µA to 5000 µA, equivalent to 0.1 mA to 5 mA (see Levine: col.5, ll.35-47) for treatment of chronic inflammatory disease intending to reverse demyelination and increase remyelination (see col.9, ll.31-42). Simon, another prior art reference in analogous art in analogous art discloses a method of reversing demyelination in a patient having a demyelinating disorder (see Abstract: electric stimulation is sufficient to encompass the intended use of “reversing demyelination” recited in this claim), the method comprising:
receiving, in a non-invasive vagus nerve stimulator (nerve stimulation device 300), a command to apply a remyelinating stimulation to the patient based on one or more biomarkers for demyelination (see [0048-0049] 300 comprises a control unit 330 for receiving command from a user or based on externally measured parameter, see [0049] “…control of the system may be based upon feedback measured from externally supplied physiological or environmental signals…”); and
applying electrical stimulation of between about 0.25 mA and about 5 mA at a duty cycle of less than 10 percent to the patient’s vagus nerve from the implanted vagus nerve stimulator to reverse demyelination and increase remyelination of the patient’s nerves ([0056:2nd sentence] a VNS therapy, e.g. current between 1 and 2mA, and a duty cycle of 10%, see [0056] and also see [0051, 0053] for adjusting stimulation duty cycle, pulse width/shape/amplitude depending on the type of disease the device is intending to treat etc.).
It would have been obvious to a person of ordinary skill in the art at the time of invention to modify Levine in view of Simon so as to adjust the stimulation to between 1 and 2mA, and a duty cycle of 10%, the motivation for doing so is because Simon explicitly states that this range is typical stimulation waveform parameter values for “invasive vagal nerve stimulation” (Simon: [0056: 1st sentence], Levin teaches invasive vagal nerve stimulation via implantable in col. col.3, ll.37-41).
Regarding claims 13-20, these claims are rejected by Levine in view of Simon as applied to claims 3-5, and 7-10 above, respectively.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Levine and Simon as applied to claim 1 above, and further in view of Ben Ezra et al. US 2005/0065553 A1 (hereinafter “Ben”, previously cited).
Regarding claim 11, Levin modified discloses the method of claim 1, but does not explicitly disclose concurrently treating the patient with a pharmacological agent to treat demyelination. Ben, a prior art reference in the analogous field of vagal nerve stimulation method and system for treatment of inflammatory demyelinating, multiple scoliosis, etc. (see Abstract) including providing an implantable stimulation device for vagal nerve stimulation, and simultaneously also administrating drug treatment ([0101, 0170 ,0120-0126]). It would have been obvious to a person of ordinary skill in the art at the time of invention to modify Levine’s stimulation treatment to further include administrating drug therapy in view of Ben, the motivation for doing so is to optimize therapeutic effects for reversing demyelination (Ben: Abstract).
Conclusion
Note to Applicant: claim 21 is not rejected under prior art rejections, the Applicant is invited to schedule an interview with the Examiner to discuss moving prosecution forward.
THIS ACTION IS MADE FINAL. 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 SHIRLEY X JIAN whose telephone number is (571)270-7374. The examiner can normally be reached M-F 8:00-4:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Benjamin Klein can be reached at 571-270-5213. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHIRLEY X JIAN/Primary Examiner, Art Unit 3792
September 10, 2026
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