DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Objections
Claims 1, 4, 7-9, 12, 14, and 16 are objected to because of the following informalities:
Claim 1:
“oligodendrocyte progenitor cells (OPCs)” in lines 3-4 should read “OPCs”
“a nerve” in line 5 should read “the nerve”
Claim 4: “stimulation per day” in line 2 should read “stimulations per day”
Claim 7: “minute” in line 2 should read “minutes”
Claim 8: “applying s electrical stimulation” in line 1 should read “applying electrical stimulation”
Claim 9:
“the level OPCs” in line 4 should read “the level of OPCs”
“a nerve” in line 5 should read “the nerve”
Claim 12: “a biosensor is configured” in line 1 should read “a biosensor that is configured”
Claim 14: “during a one or more dose sessions” in line 2 should read “during one or more dose sessions”
Claim 16: “date” in line 1 should read “day”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-8, 14, and 18 are 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.
The term “decreased level of oligodendrocyte progenitor cells” in claim 1, line 3 is a relative term which renders the claim indefinite. The term “decreased level” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear as to what the decreased level is being compared to.
Claims 2-8 are also rejected because they are dependent on claim 1.
Claim 5 recites the limitation "the repeating cycle" in line 1. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, claim 5 will be interpreted as “The method of claim 4, wherein the repeating cycle comprises waiting 5 hours, then 7 hours, then 2 hours between the application of stimulation to the nerve.”
Claim 6 recites the limitation "the vagus nerve" in line 2. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, claim 6 will be interpreted as “The method of claim 1, wherein the applied electrical stimulation is between 0.1 and 20 Hz.”
Claim 14 recites “one or more dose sessions of 5 or fewer minutes”. It is unclear as to whether the total length of the one or more dose sessions is 5 or fewer minutes, or each dose session of the one or more dose sessions is 5 or fewer minutes.
Claim 18 recites the limitations "the vagus nerve stimulator" and “the vagus nerve”. There is insufficient antecedent basis for these limitations in the claim. For the purposes of examination, claim 18 will be interpreted as “The system of claim 10, further comprising a nerve cuff configured to secure the nerve stimulator to the nerve.”
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Rennaker et al. (U.S. Patent Application Publication No. 20180085578 A1), hereinafter Rennaker, in view of McLean et al. (2014, Delayed Nerve Stimulation Promotes Axon-Protective Neurofilament Phosphorylation, Accelerates Immune Cell Clearance and Enhances Remyelination In Vivo in Focally Demyelinated Nerves. doi:10.1371/journal.pone.0110174), hereinafter McLean, and Cui et al. (Response of Human Oligodendrocyte Progenitors to Growth Factors and Axon Signals, September 2010, https://doi.org/10.1097/NEN.0b013e3181ef3be4), hereinafter Cui.
Regarding claim 1, Rennaker discloses a system for reducing demyelination and/or increasing remyelination by stimulation of a vagus nerve (paragraphs [0010], [0048], [0050], [0053], [0079], [0085]; a spinal cord injury could involve damage to myelin of affected nerves. Rennaker discloses administering a therapeutically effective amount of VNS in order to ameliorate symptoms of spinal cord injury, which includes the amount of nerve myelination) the system comprising:
applying electrical stimulation to a nerve (paragraphs [0087], [0090]) from an implanted neurostimulator (paragraphs [0010], [0082], [0085], [0087]-[0088]), wherein the applied electrical stimulation to the nerve is delivered as a charge per day of between 2.5 nC and 7.5 mC to increase the level of OPCs (paragraph [0011] discloses that the electrical signal can be a square wave; paragraphs [0098]-[0099] disclose ranges of parameters for the electrical burst stimulation train. Assuming a square wave, 1 mA pulse amplitude, 20 microsecond pulse duration, 15 pulses per burst, 25 bursts per second, 120 seconds per treatment (all within the ranges provided in paragraph [0098]), the total charge applied in one treatment is 0.9 mC, which is within the claimed range of 2.5 nC and 7.5 mC).
Although Rennaker discloses that the method reduces demyelination and/or increases remyelination (paragraphs [0010], [0048], [0050], [0053], [0079], [0085]; a spinal cord injury could involve damage to myelin of affected nerves. Rennaker discloses administering a therapeutically effective amount of VNS in order to ameliorate symptoms of spinal cord injury, which includes the amount of nerve myelination), Rennaker does not explicitly disclose identifying that a patient has a decreased level of oligodendrocyte progenitor cells (OPCs).
However, McLean teaches a method of electrical stimulation (page 2, Surgical procedures, second paragraph) that increases brain-derived neurotrophic factor (BDNF) (page 10, "Eight days post-LPC injection (3d post-ES) the ES nerves contained even higher levels of BDNF at 53.8 +/- 3.1 pg/ml (s.e.m.), as compared to the LPC-only nerves ... The levels of BDNF in the demyelination zone were still elevated in the ES-treated nerves 10d post-LPC (five days post-ES). Nerves receiving brief ES had greater BDNF IF signal and mean BDNF content (66.3 +/- 3.7 pg/ml, s.e.m.), compared to the non-stimulated LPC-treated nerves").
Cui teaches that BDNF has been shown to promote proliferation of OPCs (page 930, "In rodent cultures, several growth factors (GFs), including ... brain-derived neurotrophic factor (BDNF) promote proliferation or differentiation of OPCs derived from the CNS of neonatal animals").
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Rennaker with the teachings of McLean and Cui to identify that a patient has a decreased level of OPCs, because doing so can significantly enhance the existing intrinsic remyelination processes in vivo by increasing neuronal activity (McLean, page 15, second paragraph).
Furthermore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to limit the electrical stimulation to 2.5 nC to 7.5 mC per day, for the purpose of ensuring efficacy and safety, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
Regarding claim 6, the method of claim 1 is obvious over Rennaker, McLean, and Cui, as explained above. Rennaker further discloses that applying comprises applying electrical stimulation to the nerve at between 0.1 and 20 Hz (paragraph [0098], 1 burst per second is equivalent to 1 Hz) to the vagus nerve (paragraphs [0010], [0081]-[0082], [0088]).
Regarding claim 7, the method of claim 1 is obvious over Rennaker, McLean, and Cui, as explained above. Rennaker further discloses that applying comprises applying electrical stimulation to the nerve for less than 10 minutes each day (paragraph [0098]).
Regarding claim 8, the method of claim 1 is obvious over Rennaker, McLean, and Cui, as explained above. Rennaker further discloses that applying comprises applying electrical stimulation to the nerve from an implanted neurostimulator attached or adjacent to a vagus nerve (paragraphs [0010], [0082], [0085], [0087]-[0088]).
Claims 2, 9, 10, and 13-19 are rejected under 35 U.S.C. 103 as being unpatentable over Rennaker et al. (U.S. Patent Application Publication No. 20180085578 A1), hereinafter Rennaker, in view of McLean et al. (2014, Delayed Nerve Stimulation Promotes Axon-Protective Neurofilament Phosphorylation, Accelerates Immune Cell Clearance and Enhances Remyelination In Vivo in Focally Demyelinated Nerves. doi:10.1371/journal.pone.0110174), hereinafter McLean, and Cui et al. (Response of Human Oligodendrocyte Progenitors to Growth Factors and Axon Signals, September 2010, https://doi.org/10.1097/NEN.0b013e3181ef3be4), hereinafter Cui, and further in view of Levine et al. (US 20170203103 A1), hereinafter Levine ‘103.
Regarding claim 2, the method of claim 1 is obvious over Rennaker, McLean, and Cui, as explained above. Neither Rennaker, nor McLean, nor Cui explicitly discloses adjusting an electrical stimulation based on the level of OPCs within the patient.
However, Levine '103 teaches methods and apparatuses for electrical stimulation (Abstract) wherein the electrical stimulation is adjusted based on the level of regulatory T cells within the patient (paragraphs [0010], [0016]-[0017], [0034], [0052], [0145]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Rennaker, McLean, and Cui with the teachings of Levine '103 to adjust the electrical stimulation based on the level of OPCs within the patient, because doing so improves the efficacy of the stimulation device (Levine '103, paragraph [0005]).
Regarding claim 9, Rennaker discloses a methodfor reducing demyelination and/or increasing remyelination by stimulation of a nerve (paragraphs [0010], [0048], [0050], [0053], [0079], [0085]; a spinal cord injury could involve damage to myelin of affected nerves. Rennaker discloses administering a therapeutically effective amount of VNS in order to ameliorate symptoms of spinal cord injury, which includes the amount of nerve myelination) the system comprising:
applying electrical stimulation to a nerve (paragraphs [0087], [0090]) from an implanted neurostimulator (paragraphs [0010], [0082], [0085], [0087]-[0088]), wherein the applied electrical stimulation to the nerve is delivered as a charge per day of between 2.5 nC and 7.5 mC to increase the level of OPCs (paragraph [0011] discloses that the electrical signal can be a square wave; paragraphs [0098]-[0099] disclose ranges of parameters for the electrical burst stimulation train. Assuming a square wave, 1 mA pulse amplitude, 20 microsecond pulse duration, 15 pulses per burst, 25 bursts per second, 120 seconds per treatment (all within the ranges provided in paragraph [0098]), the total charge applied in one treatment is 0.9 mC, which is within the claimed range of 2.5 nC and 7.5 mC).
Although Rennaker discloses that the method reduces demyelination and/or increases remyelination (paragraphs [0010], [0048], [0050], [0053], [0079], [0085]; a spinal cord injury could involve damage to myelin of affected nerves. Rennaker discloses administering a therapeutically effective amount of VNS in order to ameliorate symptoms of spinal cord injury, which includes the amount of nerve myelination), Rennaker does not explicitly disclose measuring or deriving a level of OPCs within a patient, and adjusting an electrical stimulation based on the level of OPCs within the patient.
However, McLean teaches a method of electrical stimulation (page 2, Surgical procedures, second paragraph) that increases brain-derived neurotrophic factor (BDNF) (page 10, "Eight days post-LPC injection (3d post-ES) the ES nerves contained even higher levels of BDNF at 53.8 +/- 3.1 pg/ml (s.e.m.), as compared to the LPC-only nerves ... The levels of BDNF in the demyelination zone were still elevated in the ES-treated nerves 10d post-LPC (five days post-ES). Nerves receiving brief ES had greater BDNF IF signal and mean BDNF content (66.3 +/- 3.7 pg/ml, s.e.m.), compared to the non-stimulated LPC-treated nerves").
Cui teaches that BDNF has been shown to promote proliferation of OPCs (page 930, "In rodent cultures, several growth factors (GFs), including ... brain-derived neurotrophic factor (BDNF) promote proliferation or differentiation of OPCs derived from the CNS of neonatal animals").
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Rennaker with the teachings of McLean and Cui to measure or derive a level of OPCs within a patient, and adjust an electrical stimulation based on the level of OPCs within the patient, because doing so can significantly enhance the existing intrinsic remyelination processes in vivo by increasing neuronal activity (McLean, page 15, second paragraph).
Furthermore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to limit the electrical stimulation to 2.5 nC to 7.5 mC per day, for the purpose of ensuring efficacy and safety, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
Neither Rennaker, nor McLean, nor Cui explicitly discloses adjusting an electrical stimulation based on the level of OPCs within the patient.
However, Levine '103 teaches methods and apparatuses for electrical stimulation (Abstract) wherein the electrical stimulation is adjusted based on the level of regulatory T cells within the patient (paragraphs [0010], [0016]-[0017], [0034], [0052], [0145]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Rennaker, McLean, and Cui with the teachings of Levine '103 to adjust the electrical stimulation based on the level of OPCs within the patient, because doing so improves the efficacy of the stimulation device (Levine '103, paragraph [0005]).
Regarding claim 10, Rennaker discloses a system for reducing demyelination and/or increasing remyelination by stimulation of a nerve (paragraphs [0010], [0048], [0050], [0053], [0079], [0085]; a spinal cord injury could involve damage to myelin of affected nerves. Rennaker discloses administering a therapeutically effective amount of VNS in order to ameliorate symptoms of spinal cord injury, which includes the amount of nerve myelination) the system comprising:
a vagus nerve stimulator configured to be implanted over or adjacent to a vagus nerve (paragraphs [0010], [0082], [0085], [0087]-[0088]);
one or more electrodes on the vagus nerve stimulator configured to apply electrical stimulation to the vagus nerve (paragraphs [0010], [0081]-[0082], [0088]); and
a controller coupled to the nerve stimulator and configured to apply electrical stimulation to the vagus nerve from the one or more electrodes (paragraphs [0087], [0090]), wherein the controller is constrained to apply a charge per day of between 2.5 nC and 7.5 mC (paragraph [0011] discloses that the electrical signal can be a square wave; paragraphs [0098]-[0099] disclose ranges of parameters for the electrical burst stimulation train. Assuming a square wave, 1 mA pulse amplitude, 20 microsecond pulse duration, 15 pulses per burst, 25 bursts per second, 120 seconds per treatment (all within the ranges provided in paragraph [0098]), the total charge applied in one treatment is 0.9 mC, which is within the claimed range of 2.5 nC and 7.5 mC).
Although Rennaker discloses that the method reduces demyelination and/or increases remyelination (paragraphs [0010], [0048], [0050], [0053], [0079], [0085]; a spinal cord injury could involve damage to myelin of affected nerves. Rennaker discloses administering a therapeutically effective amount of VNS in order to ameliorate symptoms of spinal cord injury, which includes the amount of nerve myelination), Rennaker does not explicitly disclose measuring or deriving a level of OPCs within a patient, and adjusting an electrical stimulation based on the level of OPCs within the patient.
However, McLean teaches a method of electrical stimulation (page 2, Surgical procedures, second paragraph) that increases brain-derived neurotrophic factor (BDNF) (page 10, "Eight days post-LPC injection (3d post-ES) the ES nerves contained even higher levels of BDNF at 53.8 +/- 3.1 pg/ml (s.e.m.), as compared to the LPC-only nerves ... The levels of BDNF in the demyelination zone were still elevated in the ES-treated nerves 10d post-LPC (five days post-ES). Nerves receiving brief ES had greater BDNF IF signal and mean BDNF content (66.3 +/- 3.7 pg/ml, s.e.m.), compared to the non-stimulated LPC-treated nerves").
Cui teaches that BDNF has been shown to promote proliferation of OPCs (page 930, "In rodent cultures, several growth factors (GFs), including ... brain-derived neurotrophic factor (BDNF) promote proliferation or differentiation of OPCs derived from the CNS of neonatal animals").
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Rennaker with the teachings of McLean and Cui to measure or derive a level of OPCs within a patient, and adjust an electrical stimulation based on the level of OPCs within the patient, because doing so can significantly enhance the existing intrinsic remyelination processes in vivo by increasing neuronal activity (McLean, page 15, second paragraph).
Furthermore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to limit the electrical stimulation to 2.5 nC to 7.5 mC per day, for the purpose of ensuring efficacy and safety, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
Neither Rennaker, nor McLean, nor Cui explicitly discloses adjusting an electrical stimulation based on the level of OPCs within the patient.
However, Levine '103 teaches methods and apparatuses for electrical stimulation (Abstract) wherein the electrical stimulation is adjusted based on the level of regulatory T cells within the patient (paragraphs [0010], [0016]-[0017], [0034], [0052], [0145]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Rennaker, McLean, and Cui with the teachings of Levine '103 to adjust the electrical stimulation based on the level of OPCs within the patient, because doing so improves the efficacy of the stimulation device (Levine '103, paragraph [0005]).
Regarding claim 13, the system of claim 10 is obvious over Rennaker, McLean, Cui, and Levine, as explained above. Levine '103 further teaches that the controller is configured to deliver the electrical stimulation based on a timing of the peak levels of lymphocytes within the patient's blood (paragraphs [0008], [0101]).
Regarding claim 14, the system of claim 10 is obvious over Rennaker, McLean, Cui, and Levine, as explained above. Rennaker further discloses that the controller is configured to deliver the electrical stimulation during one or more dose sessions of 5 or fewer minutes (paragraph [0098]).
Regarding claim 15, the system of claim 10 is obvious over Rennaker, McLean, Cui, and Levine, as explained above. Rennaker further discloses that the controller is configured to apply the charge per day at a frequency between 1 and 20 Hz (paragraph [0098], 1 burst per second is equivalent to 1 Hz).
Regarding claim 16, the system of claim 10 is obvious over Rennaker, McLean, Cui, and Levine, as explained above. Rennaker further discloses that the controller is configured to apply the charge per day at a frequency between 1 and 12 Hz (paragraph [0098], 1 burst per second is equivalent to 1 Hz).
Regarding claim 17, the system of claim 10 is obvious over Rennaker, McLean, Cui, and Levine, as explained above. Rennaker further discloses that the system is configured to be implanted (paragraphs [0010], [0085], [0088]).
Regarding claim 18, the system of claim 10 is obvious over Rennaker, McLean, Cui, and Levine, as explained above. Rennaker further discloses a nerve cuff configured to secure the vagus nerve stimulator to the vagus nerve (paragraphs [0112], [0134]).
Regarding claim 19, the system of claim 10 is obvious over Rennaker, McLean, Cui, and Levine, as explained above. Rennaker further discloses that the controller is configured to apply the charge per day at two distinct frequencies between 1 and 20 Hz (paragraph [0098], the controller is capable of delivering the stimulation at any frequency between 1 and 20 Hz).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Rennaker et al. (U.S. Patent Application Publication No. 20180085578 A1), hereinafter Rennaker, in view of McLean et al. (2014, Delayed Nerve Stimulation Promotes Axon-Protective Neurofilament Phosphorylation, Accelerates Immune Cell Clearance and Enhances Remyelination In Vivo in Focally Demyelinated Nerves. doi:10.1371/journal.pone.0110174), hereinafter McLean, and Cui et al. (Response of Human Oligodendrocyte Progenitors to Growth Factors and Axon Signals, September 2010, https://doi.org/10.1097/NEN.0b013e3181ef3be4), hereinafter Cui, and further in view of Skelton et al. (US 20100280500 A1), hereinafter Skelton.
Regarding claim 3, the method of claim 1 is obvious over Rennaker, McLean, and Cui, as explained above. Neither Rennaker, nor McLean, or Cui explicitly discloses adjusting the electrical stimulation based on the time of day.
However, Skelton teaches an implantable stimulation system (Abstract) wherein the electrical stimulation is adjusted based on the time of day (paragraphs [0028], [0030], [0033], [0058]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Rennaker, McLean, and Cui with the teachings of Skelton to adjust the electrical stimulation based on the time of day, because doing so can prevent disruption of the delivery of effective stimulation therapy (Skelton, paragraph [0049]).
Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Rennaker et al. (U.S. Patent Application Publication No. 20180085578 A1), hereinafter Rennaker, in view of McLean et al. (2014, Delayed Nerve Stimulation Promotes Axon-Protective Neurofilament Phosphorylation, Accelerates Immune Cell Clearance and Enhances Remyelination In Vivo in Focally Demyelinated Nerves. doi:10.1371/journal.pone.0110174), hereinafter McLean, and Cui et al. (Response of Human Oligodendrocyte Progenitors to Growth Factors and Axon Signals, September 2010, https://doi.org/10.1097/NEN.0b013e3181ef3be4), hereinafter Cui, and further in view of Levine et al. (US 20190111263 A1), hereinafter Levine ‘263.
Regarding claim 4, the method of claim 1 is obvious over Rennaker, McLean, and Cui, as explained above. Neither Rennaker, nor McLean, nor Cui explicitly discloses that the electrical stimulation is delivered as three or more stimulations per day on a repeating cycle of waiting 5 hours or more between stimulations.
However, Levine '263 teaches systems and methods of vagus nerve stimulation to treat demyelination disorders (Abstract) wherein the electrical stimulation is delivered as three or more stimulations per day on a repeating cycle of waiting 5 hours or more between stimulations (paragraphs [0010], [0041], [0047]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Rennaker, McLean, and Cui with the teachings of Levine '263 so that he electrical stimulation is delivered as three or more stimulations per day on a repeating cycle of waiting 5 hours or more between stimulations, because doing so prevents desensitization of the nerve to the stimulation (Levine '263, paragraph [0050]).
Regarding claim 5, the method of claim 4 is obvious over Rennaker, McLean, Cui, and Levine '263, as explained above. Neither Rennaker, nor McLean, nor Cui, nor Levine '263 explicitly discloses that the repeating cycle comprises waiting 5 hours, then 7 hours, then 2 hours between the application of stimulation to the nerve.
However, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to make the repeating cycle comprise waiting 5 hours, then 7 hours, then 2 hours between the application of stimulation to the nerve, since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Rennaker et al. (U.S. Patent Application Publication No. 20180085578 A1), hereinafter Rennaker, in view of McLean et al. (2014, Delayed Nerve Stimulation Promotes Axon-Protective Neurofilament Phosphorylation, Accelerates Immune Cell Clearance and Enhances Remyelination In Vivo in Focally Demyelinated Nerves. doi:10.1371/journal.pone.0110174), hereinafter McLean, Cui et al. (Response of Human Oligodendrocyte Progenitors to Growth Factors and Axon Signals, September 2010, https://doi.org/10.1097/NEN.0b013e3181ef3be4), hereinafter Cui, and Levine et al. (US 20170203103 A1), hereinafter Levine ‘103, and further in view of Levine et al. (US 20190111263 A1), hereinafter Levine ‘263.
Regarding claim 11, the system of claim 10 is obvious over Rennaker, McLean, Cui, and Levine '103, as explained above. Neither Rennaker, nor McLean, nor Cui, nor Levine '103 explicitly discloses an input configured to receive the measured or derived level of OPCs within the patient.
However, Levine '263 teaches systems and methods of vagus nerve stimulation to treat demyelination disorders (Abstract) comprising an input configured to receive the measured or derived level of OPCs within the patient (paragraphs [0008]-[0009], [0054], [0080]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Rennaker, McLean, Cui, and Levine '103 with the teachings of Levine '263 to include an input configured to receive the measured or derived level of OPCs within the patient, because doing so enables the system to apply stimulation to the nerve when the biosensor detects a biomarker indicative of demyelination (Levine '263, paragraph [0083]).
Regarding claim 12, the system of claim 10 is obvious over Rennaker, McLean, Cui, and Levine '103, as explained above. Neither Rennaker, nor McLean, nor Cui, nor Levine '103 explicitly discloses a biosensor that is configured to detect a marker for the level of OPCs within the patient.
However, Levine '263 teaches systems and methods of vagus nerve stimulation to treat demyelination disorders (Abstract) comprising a biosensor that is configured to detect a marker for the level of OPCs within the patient (paragraphs [0008]-[0009], [0054], [0080]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Rennaker, McLean, Cui, and Levine '103 with the teachings of Levine '263 to include a biosensor that is configured to detect a marker for the level of OPCs within the patient, because doing so enables the system to apply stimulation to the nerve when the biosensor detects a biomarker indicative of demyelination (Levine '263, paragraph [0083]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINE SISON whose telephone number is (703)756-4661. The examiner can normally be reached 8 am - 5 pm PT, Mon - Fri.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer McDonald can be reached at (571) 270-3061. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHRISTINE SISON/Examiner, Art Unit 3796
/REX R HOLMES/Primary Examiner, Art Unit 3796