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 10/13/2017 according to the priority chain on the record.
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 1-4 and 6-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 9-16, 19 and 20 of copending Application No. 18/664817 (reference application). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because the current application discloses a method comprising substantially the same steps as the claimed invention of the copending application (app’817), italicized limitations below:
Current application 19/224699
Copending app’817 (as received on 06/22/2026)
1. A method of treating multiple sclerosis (MS), the method comprising:
receiving, in an implanted vagus nerve stimulator implanted in a patient, a command to apply a remyelinating stimulation to a patient; 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 to treat the patient's MS.
1. (Currently Amended) A method of reversing demyelination in a patient having a demyelinating disorder, the method comprising:
receiving, in an implanted vagus nerve stimulator, a command to apply a remyelinating stimulation to the patient based on one or more biomarkers for indicating demyelination; and
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.
2. The method of claim 1, wherein applying comprises applying the electrical stimulation, followed by an off-time of at least 10 minutes.
2. (Original) The method of claim 1, wherein applying comprises applying the electrical stimulation, followed by an off-time of at least 10 minutes.
3. The method of claim 1, wherein applying comprises applying the electrical stimulation for less than about 2 minutes.
3. (Previously Presented) The method of claim 1, wherein applying comprises applying the electrical stimulation for less than 2 minutes.
4. The method of claim 1, wherein applying comprises applying the electrical stimulation for less than about 2 minutes, followed by an off-time of at least 10 minutes.
4. (Previously Presented) 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.
6. The method of claim 1, further comprising monitoring one or more biomarkers for demyelination.
6. (Original) The method of claim 1, further comprising detecting the one or more biomarkers for demyelination.
7. 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.
9. (Original) 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 CD163, 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.
8. The method of claim 1, further comprising repeatedly applying a low duty-cycle electrical stimulation of between about 0.25 and about 5 mA to the patient's vagus nerve for less than 2 minutes, followed by an off-time of between about 12 and about 48 hours.
10. (Previously Presented) 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, followed by an off-time of between-12 and 48 hours.
9. The method of claim 1, further comprising concurrently treating the patient with a pharmacological agent to treat demyelination.
11. (Original) The method of claim 1, further comprising concurrently treating the patient with a pharmacological agent to treat demyelination.
10. A method of treating MS by reversing demyelination in a patient having MS, the method comprising:
receiving, in an implanted vagus nerve stimulator in a patient diagnosed with MS, a command to apply a remyelinating stimulation to the patient; 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.
12. (Currently Amended) A method of reversing demyelination in a patient having a demyelinating disorder, the method comprising:
detecting one or more biomarkers for demyelination from the patient;
receiving, in an implanted vagus nerve stimulator, a command to apply a remyelinating stimulation to the patient based on a level of the detected one or more biomarkers for indicating demyelination; and
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.
11. The method of claim 10, wherein applying comprises applying the electrical stimulation, followed by an off-time of at least 10 minutes.
13. (Original) The method of claim 12, wherein applying comprises applying the electrical stimulation, followed by an off-time of at least 10 minutes.
12. The method of claim 10, wherein applying comprises applying the electrical stimulation for less than about 2 minutes.
14. (Previously Presented) The method of claim 12, wherein applying comprises applying the electrical stimulation for less than 2 minutes
13. The method of claim 10, wherein applying comprises applying the electrical stimulation for less than about 2 minutes, followed by an off-time of at least 10 minutes.
15. (Previously Presented) The method of claim 12, wherein applying comprises applying the electrical stimulation for less than 2 minutes, followed by an off-time of at least 10 minutes.
14. The method of claim 10, further comprising monitoring the patient for the one or more biomarkers for demyelination.
16. (Original) The method of claim 12, further comprising continuously monitoring the patient for the one or more biomarkers for demyelination.
15. The method of claim 14, 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.
19. (Original) The method of claim 12, wherein the one or more biomarkers for demyelination is selected from the group consisting of neurofilament, glial fibrillary acidic protein, the monocyte macrophage marker CD163, 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.
16. The method of claim 10, further comprising repeatedly applying a low duty-cycle electrical of between about 0.25 and about 5 mA to the patient's vagus nerve for less than 2 minutes, followed by an off-time of between about 12 and about 48 hours.
20. (Previously Presented) The method of claim 12, 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, followed by an off-time of between 12 and-48 hours.
As shown in the italicized limitations above, the current application and the copending application essentially disclose methods which are not patentably indistinguishable from another, except for different intended uses disclosed in respective preambles. That is, the current application is intended for MS treatment, while the copending application is intended for remyelination. Since it is known in the medical field that MS is characterized by demyelination which is represented/indicated by substantially the same biomarkers (see app. 5-6, 9, 16 and 19). In this rejection, the preambles are not given patentable weight as they are treated as intended use/functional language of applying the recited method steps.
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, which are taken as intended use/functional limitation of applying the recited methos steps. 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.
Drawings
The drawings are objected to because Figs. 15B, 16A, 16C, 16E, 17A, 17B, 18A and 18B include graphics that are very dark and do not show any/sufficient details. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 7 and 15 are objected to because of the following informalities: in the list of biomarkers recited in these claim “the monocyte macrophage marker CD 163”, “the glial activation marker YKL-40” and “the B cell chemoattractant CXCL13” appear to be typographical errors. Appropriate correction is required.
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 1-5, 8, 10-14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Levine et al. US 8,788,034 B2 (hereinafter “Levine”) 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 treating multiple sclerosis (MS) (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.40 lists multiple sclerosis as an example of inflammatory disorder treatable by the disclosed invention), the method comprising:
receiving, in an implanted vagus nerve stimulator implanted in a patient (col.3, ll.39-40 implanting into a patient’s vagus nerve a 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 a patient (col.2, ll.5-57 and col.4, ll.15-50 applying a stimulation to the vagus nerve for treatment of multiple sclerosis, which is presented with demyelination; this meets the intended use of “remyelinating”).
Levine discloses a method to treat the patient’s MS, but Levine does not explicitly disclose 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. 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, 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 about 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 about 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 MS. (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...”, cytokine is a biomarker for MS according to the Applicant’s own Specification [0073])
Regarding claim 6, Levine modified discloses the method of claim 1, further comprising monitoring one or more biomarkers for demyelination. (Levine: col.9, ll.33-36 cytokine is a biomarker for demyelination)
Regarding claim 8, Levine modified discloses the method of claim 1, further comprising repeatedly applying a low duty-cycle electrical stimulation of between about 0.25 and about 5 mA to the patient's vagus nerve for less than 2 minutes, followed by an off-time of between about 12 and about 48 hours. (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 claims 10-14 and 16, these claims are rejected by Levine in view of Simon under the same rationale as discussed to claims 1-6, and 8 above.
To claim 10, Levine discloses a method of treating MS by reversing demyelination in a patient having MS (see col.4, ll.40 lists multiple sclerosis as an example of inflammatory disorder treatable by the disclosed invention).
Claims 7 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Levine and Simon as applied to claims 6 or 14 above, and further in view of Kantor et al. US 2015/0031562 A1 (hereinafter “Kantor”, previously cited).
Regarding claim 7, Levine modified discloses the method of claim 6, Levine discloses a method and system adapted for treating multiple sclerosis (col.4, ll.40 lists multiple sclerosis as an example of inflammatory disorder treatable by the disclosed invention), and discloses monitoring biomarkers indicative of chronic inflammation (col.10, ll.13-17 TNF and sirtuin levels, cytokine levels), but does not explicitly disclose 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.
Kantor, another prior art reference, discloses a method for monitoring biomarkers for multiple sclerosis including at least: monocyte-associated variable ([0012]), B cell chemoattractant ([0012, 0024, 0171]), macrophages markers ([0377, 0416-0417]), and mRNA ([0199, 0229]). It would have been obvious to a person of ordinary skill in the art at the time of invention to further modify Levine in view of Kantor to include detecting different biomarkers indicative of MS, the motivation for doing so is evaluate the efficacy of the applied electrical stimulation therapy with respect to MS treatment based on biomarker levels (Levine: col.9, ll.39-42 “…the systems described herein may include a sensor and/or data processing subsystem for monitoring the patient and/or the effect of the treatment with the system.”).
Claim 15 is rejected by Levine, Simon in view of Kantor under the same rationale as discussed to claim 7 above.
Claim 9 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 9, Levine in view of Simon 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
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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/SHIRLEY X JIAN/Primary Examiner, Art Unit 3792
September 27, 2026
