The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Response to Arguments
Applicant's arguments filed June 22, 2026 have been fully considered but they are not persuasive. On pages 6-7 of the remarks, the applicant argues that “Tang-Schomer fails to teach an in vivo method of applying an alternating electric field to a target site of a subject in order to treat spinal cord injury as in claim 1 or to increase axon regeneration in a subject as in claim 6. The entire disclosure of Tang-Schomer describes applying an alternating electric field to cultured neuronal cells obtained from a subject.” The applicant then discusses “that paragraph 101 of Tang-Schomer, which is cited in the Office Action, states ‘[w]hile most of the neuronal cells are differentiated as produced by the presently disclosed method, when the neuronal cells are not differentiated prior to transplant, the neuronal cells can proliferate up to two to four cell divisions in vivo before differentiating, thereby further increasing the number of effective donor cells.’"
In paragraph 101, there is discussion of cells that differentiate in vivo. Additionally, the previous Office action states on page 3, “see paragraph 114 for discussion of treating a spinal cord and paragraph 118 for discussion of applying electric field to neuronal cells in a subject”. More specifically, paragraph 114 states “introducing the therapeutically effective amount of the neuronal cell population may include injecting at least a portion of the therapeutically effective amount into a plurality of areas of the recipient spinal cord”, which teaches treatments being used for treating the spinal cord. Additionally, paragraph 118 states “the method of treatment comprises applying electric field of alternating polarity and changing frequencies directly to neuronal cells in a subject.” Therefore, paragraph 118 explicitly teaches the application of an alternating electric field directly to the neuronal cells in a subject. In addition to this, paragraph 15 states “Provided herein is a method to modulate directed growth of neuronal axon comprising applying an alternating field electrical signal to a neuronal cell comprising an axon in a subject for a period of time.” And paragraph 69 teaches the following, which teaches an embodiment in which electrical fields are applied in vivo:
In certain embodiments, the field intensity in an in vivo system is 200-300 μV/mm, 300-400 μV/mm, 400-500 μV/mm. In certain embodiments, the duration is 1-2 weeks, 2-3 weeks, 3-4 weeks, 4-6 weeks, 6-8 weeks, 8-10 weeks, 10-12 weeks, 12-15 weeks. In one embodiment, the field intensity and duration is 200 μV/mm for up to 4 weeks. In one embodiment, the oscillating electric fields is 500-600 μV/mm for 18 days. In one embodiment the oscillating electric fields is 500-600 μV/mm, 15-min on/15-min off, for up to 15 weeks. In certain embodiments, the electric current is directly applied to live neurons and live systems.
For at least these reasons, the applicant’s arguments are not persuasive and the rejections are maintained and provided again below.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-10, 12, 14-16 and 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tang-Schomer (US Patent Pub. No. 2019/0105498).
Regarding claims 1 and 7, Tang-Schomer discloses a “method of modulating modulate directed growth of neuronal axon by applying an alternating field electrical signal” (see Abstract). Particularly, Tang-Schomer teaches applying an alternating electric field (see paragraph 7, “We have now surprisingly found a method of controlling neuronal network synchrony by applying an alternating electrical field to living neurons), at a frequency for a period of time (see paragraph 12, “Provided herein is a method … comprising applying an alternating EF to a neuronal network of neuronal cell in a 3D culture for a period of time, wherein the EF comprises one or more frequencies”), to a target site of the subject (see paragraph 101, which teaches the methods may be used in vivo; also see at least paragraph 118 for discussion of applying electric field to neuronal cells in a subject), wherein the target site is at the site of a spinal cord injury (see paragraph 98, “The present method comprises the step of administering the composition to a subject (e.g., a patient)… Cell therapy has been used to repair spinal cord injuries”; see paragraph 114 for discussion of treating a spinal cord and paragraph 118 for discussion of applying electric field to neuronal cells in a subject).
Regarding claim 2, it is noted that the method of claim 1 is taught by the prior art. Claim 2 simply adds that the application of the alternating electric field [of claim 1] results in a specific effect (i.e., increases N-cadherin expression at the target site). Since the method steps of claims 1 and 2 are taught by the prior art, the result of such method steps will inherently result in the same claimed effect of claim 2, absent some specifically claimed step that causes the effect stated in claim 2. Therefore, the presently recited claims are taught by Tang-Schomer.
Regarding claim 3, Tang-Schomer teaches that “the presently disclosed method provides a 3D culturing condition subjected to an alternating electric field where the neuronal axon has a growth of about 10-20%, about 20-30%, about 30-40% more in length compared to the axons of un-stimulated neurons” (see paragraph 9).
Regarding claim 4, Tang-Schomer teaches that “Neuronal cells can be prompted to project into ventral roots and innervate muscle where they engage in extensive reciprocal connections with host motor neurons in subjects with degenerative motor neuron disease” (see paragraph 106).
Regarding claim 5, Tang-Schomer teaches applying alternating electric fields (see paragraph 7, “We have now surprisingly found a method of controlling neuronal network synchrony by applying an alternating electrical field to living neurons), at a frequency for a period of time (see paragraph 12, “Provided herein is a method … comprising applying an alternating EF to a neuronal network of neuronal cell in a 3D culture for a period of time, wherein the EF comprises one or more frequencies”), to a target site of the subject (see paragraph 101, which teaches the methods may be used in vivo; also see at least paragraph 118 for discussion of applying electric field to neuronal cells in a subject), thereby increasing N-cadherin expression at the target site of the subject (it is noted that this “thereby” statement does not present a further step to the claimed method, but instead recites a result of the positively recited step of applying an AC electrical field to a target site at a frequency and a period of time. Therefore, the result of the positively claimed method step(s) will inherently result in the same claimed effect of the “thereby” statement, absent some specifically claimed step that causes this specific effect. Therefore, the presently recited claim is taught by Tang-Schomer).
Regarding claim 6, Tang-Schomer teaches applying alternating electric fields (see paragraph 7, “We have now surprisingly found a method of controlling neuronal network synchrony by applying an alternating electrical field to living neurons), at a frequency for a period of time (see paragraph 12, “Provided herein is a method … comprising applying an alternating EF to a neuronal network of neuronal cell in a 3D culture for a period of time, wherein the EF comprises one or more frequencies”), to a target site of the subject (see paragraph 101, which teaches the methods may be used in vivo; also see at least paragraph 118 for discussion of applying electric field to neuronal cells in a subject), thereby increasing axon regeneration at the target site of the subject (see paragraph 9, “the presently disclosed method provides a 3D culturing condition subjected to an alternating electric field where the neuronal axon has a growth of about 10-20%, about 20-30%, about 30-40% more in length compared to the axons of un-stimulated neurons”).
Regarding claim 8, Tang-Schomer teaches the use of a linear ordered collagen scaffold (see paragraphs 169-170).
Regarding claim 9, it is noted that claim 9 recites that “the spinal cord injury occurred at least 1 day before applying the alternating electric field”. It is also noted that Tang-Schomer teaches in its claim 8 that “the neuronal cells were cultured for about 1-3 weeks before the EF was applied.” As such, Tang-Schomer inherently reads on there being at least 1 day before applying the alternating electric field (i.e., at least 7 days since “about 1 week” is “about 7 days”).
Regarding claim 10, Tang-Schomer teaches that “In certain embodiments, the present composition may further comprise… steroid hormones” (see paragraph 83), thereby teaching administering steroid treatment as claimed.
Regarding claim 12, Tang-Schomer teaches the use of a range of frequencies including about 0.2 Hz to about 200 kHz (see paragraph 12-13).
Regarding claims 14-15, Tang-Schomer teaches that “In certain embodiments, the electric field setup generated a theoretical EF strength of about 0.1-15 mV/mm” (see paragraph 67; noting that 1 mV/mm = 1 V/cm).
Regarding claim 16, Tang-Schomer teaches that “the presently disclosed method provides a 3D culturing condition subjected to an alternating electric field where the neuronal axon has a growth of about 10-20%, about 20-30%, about 30-40% more in length compared to the axons of un-stimulated neurons” (see paragraph 9).
Regarding claims 19-20, Tang-Schomer teaches that “a variety of conditions can be treated by the disclosed methods because of the ability of the implanted cells to generate neurons in vivo” (see paragraph 101; also see at least paragraph 118 for discussion of applying electric field to neuronal cells in a subject), and paragraph 111 also discusses grafting of neuronal cells. Additionally, paragraph 169 discusses a silk protein material-based scaffold that is infused with an extracellular matrix (ECM) gel, such as collagen type I gel. Additionally, Tang-Schomer teaches that “The present method comprises the step of administering the composition to a subject (e.g., a patient)… Cell therapy has been used to repair spinal cord injuries” (see paragraph 98).
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 11, 13 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Tang-Schomer alone.
Regarding claim 11, Tang-Schomer is described above with regard to claim 1. It is noted that the entire disclosure of Tang-Schomer makes no mention of the patient having cancer or not having cancer. As such, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application that the methods and treatment techniques proposed by Tang-Schomer would and could be used on a patient who “does not have cancer, has not been diagnosed with cancer, or is not being treated for cancer”.
Regarding claim 13, Tang-Schomer is described above with regard to claim 1. Tang-Schomer teaches the use of a range of frequencies including about 0.2 Hz to about 200 kHz (see paragraph 12-13). It is noted that “about 200 kHz” is not a hard upper limit, and may comprise upward of, for instance, 210 kHz. And also it is noted that it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to utilize frequencies at the bottom of the claimed range of 210-400 kHz based on the teachings of Tang-Schomer, 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 USPC 233 (see MPEP 2144.05(II)(A)).
Regarding claim 18, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to stop applying treatment to a patient once the desired outcome of the treatment has been reached. In this case, the treatment being the application of an alternating electrical field for the purpose of restoring connectivity at the site of a spinal injury.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Tang-Schomer as applied to claim 1 above, and further in view of Matos et al. (“Alternating Current Electric Field Effects on Neural Stem Cell Viability and Differentiation”, published 2010).
Tang-Schomer is described above with respect to claim 1. While cell differentiation is discussed throughout Tang-Schomer with regard to the stem cells, there is no explicit teaching of increased cell differentiation due to the electric field.
Matos teaches that “Cell viability and differentiation was studied as a function of electric field magnitude and frequency” (see Abstract). It states that “we focus on the effects of low amplitude alternating current (AC) electric fields on neural stem cell viability and differentiation” (see last paragraph on right side of page 664). Matos concluded that an applied electric field as studied can significantly impact neural stem cell behavior, including differentiation (see pages 668-669).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application that alternating current electrical stimulation, as applied in both Matos and Tang-Schomer, to stem cells would improve differentiation, as this is evidenced by Matos and the similar application of an alternating electric field in Tang-Schomer would have the same effect.
Conclusion
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 JAMES KISH whose telephone number is (571)272-5554. The examiner can normally be reached M-F 10:00a - 6p EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Unsu Jung can be reached at (571) 272-8506. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMES KISH/ Primary Examiner, Art Unit 3792
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