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
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 7 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 7 recites “wherein the target site is a site of a spinal cord injury”. However, claim 1 already recites “wherein the target site is at the site of the spinal cord injury”. Therefore, claim 7 is an improper dependent form for failing to further limit the subject matter of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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), 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), 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), 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), 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
The following prior art is herein made of record is considered pertinent to applicant's disclosure, but not relied upon in the rejections above:
Graves et al., “Electrically Mediated Neuronal Guidance with Applied Alternating
Current Electric Fields”, published February 2011.
“To date, most of this research has focused on the application of a direct current (DC) stimulus to produce the desired EF and induce neuronal growth. We propose that high duty-cycle alternating current (AC) stimulation is capable of inducing similar EFs within the spinal cord” - Abstract
Cheng et al., “Electrical Stimulation Promotes Stem Cell Neural
Differentiation in Tissue Engineering”, published 2021.
Nerve injuries and neurodegenerative disorders remain serious challenges, owing to the poor treatment outcomes of in situ neural stem cell regeneration. The most promising treatment for such injuries and disorders is stem cell-based therapies, but there remain obstacles in controlling the differentiation of stem cells into fully functional neuronal cells. … we summarize the most basic waveforms of electrical stimulation and the conductive materials used for the fabrication of electroactive substrates or scaffolds in neural tissue engineering… Finally, we also discuss the possible mechanisms in enhancing stem cell neural differentiation using electrical stimulation” - Abstract
Tong-Schomer, “3D axon growth by exogenous electrical stimulus and soluble factors”, published 2017.
The present study investigates the effects of exogenous stimulus of electrical signals and soluble factors on axon 3D growth, using a silk protein material-based 3D brain tissue model” - Abstract
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/JAMES KISH/ Primary Examiner, Art Unit 3792