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 .
Information Disclosure Statement
The information disclosure statement filed September 2, 2022 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
No copy of NPL document #46 has been found.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-4, 6, 8-9, 13-14, 16-18, 20-22, 26, 29-30, 32, 37, 41-43, 45, and 47-58in the reply filed on June 6, 2025 is acknowledged.
Claims 59-61 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Interpretation
Content of Specification
(k) CLAIM OR CLAIMS: See 37 CFR 1.75 and MPEP § 608.01(m). The claim or claims must commence on a separate sheet or electronic page (37 CFR 1.52(b)(3)). Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation. There may be plural indentations to further segregate subcombinations or related steps. See 37 CFR 1.75 and MPEP 608.01(i)-(p).
The claimed invention is defined by the positively claimed elements, the structural elements listed on separate indented lines listed in the body of the claim after the transitional phrase, “comprising”.
A claim is only limited by positively claimed elements. Thus, "[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims”. MPEP 2115 Material or Article Worked Upon by Apparatus.
It is noted that the apparatus claims 1 (and dependent claims) mention a microengineered physiological system, micropatterned platform, and neural architecture. However, none of the prior are positively claimed as structural elements of the invention, an apparatus. Therefore, none of such structural define the claimed apparatus. All of such are considered as articles and/or materials intended to be worked upon and used with the apparatus.
It is noted that a two-dimensional electrode and a three-dimensional electrode are not specifically defined in claim 1. It is presumed that an electrode that has at least two dimensions (length, width, diameter, height, etc.) is considered a two dimensional electrode and an electrode that has at least three dimensions is a three dimensional electrode. It is noted that three-dimensional electrode is also a two-dimensional electrode.
It is noted that the phrases “at least one” and “one or more” only require 1.
It is noted that the term “or” provides for alternative options, not requirements.
It is noted that the various “configured to…” clauses recited throughout the claims do not provide for any further structural element, but are directed to intended use. Placing the phrase “configured to…” before possible uses of structures does not provide for any further structure of the respective structures and invention.
It is noted that the term “plurality” only requires 2.
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 1-4, 6, 8-9, 13-14, 16-18, 20-22, 26, 29-30, 32, 37, 41-43, 45, and 47-58 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.
It is noted that the claims are replete with awkward, ambiguous, vague, and confusing language. The examiner has attempted to identify each of the issues of the claims, but requests applicant correct any issues inadvertently omitted herein.
As to claims 1-4, 6, 8-9, 13-14, 16-18, 20-22, 26, 29-30, 32, 37, 41-43, 45, 55, and 57-58, it presumed that the phrase “the microelectrode array” refers to “the three-dimensional array”. If so, for consistency the claims should clearly recite such.
As stated above, the last paragraph of claim 1 does not provide for any further structure of the apparatus because no detection of any signals is required to be performed with any unclaimed microengineered physiological system. It is unclear what is considered “one or more biological signals” because such are not defined in the claim. Also applicable to claims 2 and 13-14.
The term “reliable” in claim 1 is a relative term which renders the claim indefinite. The term “reliable” 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. Although no detection is required to performed, what may be considered as “reliable” detection to one person may not be considered as such to another.
Although a microengineered physiological system is not positively claimed as an element of the invention, it is unclear what is structurally considered a microengineered physiological system because the does not define such by any specific structural elements.
Dependent claims 2-4, 6, 8-9, 13-14, 16-18, 20-22, 26, 29-30, 32, 37, 41-43, 45, and 47-58 are rejected via dependency upon a rejected claim.
It is unclear what is further structurally required by claim 2 because the claim does not provide for any further structural element nor any further structure of any prior positively claimed element. The claim is directed to signals (not structure). Furthermore, each of the signals are not defined in the claim. Therefore, it unclear what constitutes, is considered as each of the signals.
The term “high frequency waves” and “low frequency waves” in claim 2 is a relative term which renders the claim indefinite. The term ““high frequency waves” and “low frequency waves”” 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. What frequency values that by be considered as “high” and “low” to one person may not be considered as such to another and vice versa.
As to claim 3, it is unclear what is further structurally required by the claim because the claim does not provide for any further structural element nor limits and previously positively claimed structural element. The is directed to the unclaimed microengineered physiological system. This is also applicant to claims and portions of claims 4, 14, 21, and 30 directed to the microengineered physiological system. The same is applicable to the neural architecture in claims 4.
Although the micropatterned platform of claim 4 is not structurally defined and not positively claimed as an element of the invention, it is unclear what structurally required by the “permits…” clause. What the structure “permits” does not provide for a structural element.
As to claim 4 it is unclear what structurally required by the last paragraph because the claim is directed to the entire device and not any specific prior claimed structural element. It is unclear what structural connectivity of the area to the prior claimed chip, at least one two-dimensional electrode, and at least one three-dimensional electrode because the claim does not provide for such.
It is unclear what is the structural connectivity of the positively claimed elements because none of the recited elements are required to be structurally connected to each other so as to define a single apparatus. A list of parts that are not required to be structurally connected do not define a single apparatus. Therefore, it is unclear how the claims as drafted are considered to define a single apparatus.
Furthermore it is unclear what is structurally an “area” because such area is not defined by any specific structure, structural boundaries or dimensions so as to determine where such area begins and ends so as to distinguish such area from any other area or structures. It is also unclear what is structured required of such area to have configuration that is complementary to that of the neural architecture because such area configuration is not structurally defined. As previously noted above the neural architecture is not a structural element of the invention and such is not structural define as having and structurally defined configuration.
As to claims 6 and 8, it is unclear what is the structural nexus and/or connectivity of the first plurality of electrodes and second plurality of electrodes to each other and to the at least one two-dimensional electrode and at least one three-dimensional electrode of claim 1. See prior rejection of claim 4 above directed to lack of structural connectivity. It is unclear if the at least one two-dimensional electrode and at least one three-dimensional electrode are included with either of the first or second plurality of electrodes or are different from such because the claim does not recite such.
Claim 6 recites the limitations " the ganglion region or spheroid region” and “the axonal growth region”. There is insufficient antecedent basis for this limitation in the claim. Furthermore, it is unclear what is structurally required to define each of such “regions” because such are not defined by any specific structure, structural boundaries or dimensions so as to determine where each such begins and ends so as to distinguish each region form each other and from any other region or structures. Therefore, it is also unclear what is structurally meant by, considered as “down” the axonal growth region because no structural basis is provided to indicate what/which direction is structurally considered as such.
It is noted that the term plurality only requires 2. Therefore, 2 electrodes would only provide for a single distance (interval) between such.
The term “about” in claims 9, 22, and 32 is a relative term which renders the claim indefinite. The term “about” 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. There is no indication as what variations from the specific values are considered “about” the specific values recited in the claims. What may be considered “about” the specific values to one person may not be considered as such to another and vice versa.
As to claims 13-14, it is unclear what is structurally required by the claims because the claims do not provide for any additional structural element nor further limit any prior positively claimed elements. Instead the claim is directed to what the entire invention, the three-dimensional microelectrode array can possibly be used to do.
As to claim 16, it is unclear what is the structural connectivity of the biocompatible, ink, paste, and composite to the prior positively claimed elements of claim 1 because the claim does not provide for such. Furthermore, it is noted the recited ink, paste, and composite are not mutually exclusive. . See prior rejection of claim 4 above directed to lack of structural connectivity.
As to claims 17-18, it is unclear what is the structural connectivity of the one or vias and insulation layer to the prior positively claimed elements of claim 1 because the claims do not provide for such. See prior rejection of claim 4 above directed to lack of structural connectivity.
As to claim 20, it is unclear what is the structural connectivity of the volumetric stimulators to the prior positively claimed elements of claim 1 and structurally required to be considered a volumetric stimulator because the claim does not provide for such. See prior rejection of claim 4 above directed to lack of structural connectivity.
As to claim 22, it is unclear what is the structural connectivity of the various “at least one electrode” to the prior positively claimed elements of claim 1 the at least one two-dimensional electrode and at least one three-dimensional electrode and if each “at least one electrode” recited in the claim is the same or different because the claim does not provide for such. See prior rejection of claim 4 above directed to lack of structural connectivity.
Claim 29 recites the limitation "the microelectrode arrays". There is insufficient antecedent basis for this limitation in the claim. Furthermore, it is unclear what is structurally required by the claim because the claims do not provide for any additional structural element nor further limit any prior positively claimed elements. Instead the claim is directed to what the entire invention, the three-dimensional microelectrode array can possibly be used to do.
As to claim 30, it is presumed the phrase “with a structure” means “comprises a structure. If so, the claim should clearly recite such. Furthermore, it is unclear what is required structurally required of a structure to be considered as analogous to peripheral never anatomy because the claim does not provide for such.
As to claim 32, it is unclear what is the structural connectivity of the various “at least one three-dimensional electrode” to the prior positively claimed elements of claim 1 and “the at least one three-dimensional electrode and it is unclear if each “at least one three-dimensional electrode” recited in the claim is the same or different because the claim does not provide for such. See prior rejection of claim 4 above directed to lack of structural connectivity.
As to claim 37, it is unclear what is structurally required by the claim because the claim does not provide for any additional structural element nor further limit any prior positively claimed elements. Instead the claim is directed to what the entire invention, the three-dimensional microelectrode array can possibly be used to do. Furthermore, it is unclear what is structurally considered as “inference” and what each item in the list is meant to be a property of because the claim does not recite such. It is further unclear what is “integral”, “threshold”, and what is intended to measured after compound administration (to what) does not provide for any further structural element. There is no requirement for any process step to performed such a broad, unspecified compound is administered to anything. Furthermore, it is unclear what the acronym CAP means because the claim does not provide for such.
As to claim 41, it is unclear what is the structural connectivity of the various items (layers and micro-towers) to the prior positively claimed elements of claim 1, the chip, the at least one two-dimensional electrode, and at least one three-dimensional electrode and it is unclear what is structurally required to define a conductive trace layer and micro-towers because the claim does not provide for such. See prior rejection of claim 4 above directed to lack of structural connectivity.
Claim 42 recites the limitation "the at least one micro-tower" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 41 previously recites micro-towers. However, such are an option not a requirement. Therefore, claim 42 is only limiting if micro-towers is selected as an option.
As to claim 43, it is unclear what is the structural connectivity of the various items (titanium/gold metal trace and respective layers) to the prior positively claimed elements of claim 1, the chip, the at least one two-dimensional electrode, and at least one three-dimensional electrode and it is unclear what is structurally required to define a titanium/gold metal trace and the respective layers because the claim does not provide for such. See prior rejection of claim 4 above directed to lack of structural connectivity.
As to claims 45 and 47-49 it is unclear, which/what system is being referenced by the phrase “the system” because claims 1 and 45 previously recites “microengineered physiological system” and claim 45 recites “a system”. As to claims 47-49, it is noted that claim 45 also recites “a microphysical system” which also makes it unclear which/what system is being referenced by “the system”. Furthermore it is unclear what is the nexus of “microengineered physiological system” recited in claim 45 and “a microengineered physiological system” recited in claim 1. It is unclear if such are the same or different because the claim does not provide for such. Furthermore, it is unclear what/which microelectrode array is being referenced by “the microelectrode array” because claim 1 recites “a three-dimensional microelectrode array” and claim 45 previously recites “a microelectrode array”. Furthermore, it is noted that the microphysical system is only structurally defined as one or more neuronal cells, which only requires 1 neuronal cell.
It is noted that claim 49 is only further limiting if peripheral nervous system neurons is selected as the option from the list of alternative options of claim 47.
It is noted that it is not specified in the method claims 50-58 who and/or what is required to perform each of the method steps.
It is noted that claims 50, 55, and 57-58 do not further structurally limit the apparatus, array of claim 1.
As to claim 50 and 53, it is unclear what is structurally required to define each of the axonal growth region and ganglion region because such are not defined by any specific structure(s), structural boundaries or dimensions so as to determine where each such begins and ends so as to distinguish each region form each other and from any other region or structures. Therefore, it is also unclear what is structurally meant by, considered as “along” the axonal growth region, the growth region because no structural basis is provided to indicate what/which direction is structurally considered as such. Furthermore, it is noted that the claim does not specify to what structural element of the [three-dimensional] array the neural tissue is transferred to in the second alternative, option. See also claims 55 and 57-58.
Claim 50 recites the limitation " the nerve conduction velocity of the sample neural tissue" in the paragraph beginning with “electrophysiological testing…”. There is insufficient antecedent basis for this limitation in the claim.
The term “healthy” in claim 50 is a relative term which renders the claim indefinite. The term “healthy” 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. What tissue may be considered as healthy to one person may not be considered as such to another and vice versa.
As to claim 51, it is presumed that the claim is intended to provide for a step of performing histological analysis. If so, the claim should clearly recite such. Furthermore, it is noted that the claim does not specify what is required to be done by who or what to perform such nor when such step is required to occur relative to the steps of claim 50.
As to claim 51, it is unclear which what neural tissue is being reference by “the neural tissue” because claim 50 previously recites “sample neural tissue”, “transferring neural tissue”, and “healthy neural tissue”.
As to claim 52, it is unclear what property of what is each of the items in the list of alternatives are properties of because the claim does not recite such. Furthermore, it is noted that it is not specified what is considered as “am assessment” and what is required to be done by who or what to define such.
As to claim 53, it is unclear if “stimulating” is the same or different from “electrically stimulating” in claim 50 because the claim does not provide for such. Furthermore, it is noted that “recording” (in claims 50 and 53) is not specified as being done by any structure nor person (mentally or manually).
As to claim 54, it is unclear what neurodegeneration of what is required to be measured because the claim does not recite such.
As to claim 55, it is unclear what is required to be transferred to the microelectrode array in the second alternative because the claim does recite such. Furthermore, as to the “wherein” paragraph it is unclear what each of the items in the list are properties of because the claim does not recite such.
As to claim 56, it is noted that each of the items of the list are not mutually exclusive. For example, the prior recited stimulus/stimuli recited before “physical stimuli” can be considered as “physical stimuli” and “optical stimuli” can be electrical stimulus and vice versa.
Claim 57 recites the limitation "the toxicity of an agent" in line 1. There is insufficient antecedent basis for this limitation in the claim. It is unclear what is the nexus of “at least one agent” recited in the exposing step to “an agent” recited in the preamble because the claim does not recite such. Therefore, it is also unclear which what agent is being referenced by the phrase “the agent” recited in the claim. Furthermore, it is noted that it is not specified what is meant by “exposing”. It is noted that such does not require any physical contact of the at least one agent and the neural tissue. It is noted that the measuring, observing, and correlating can be done visually and/or mentally. However, it is unclear what each of the items in the list recited in the “measuring” paragraph are properties of because the claim does not recite such. Furthermore, it is unclear what changes (what measurement values and what has to be observed) is considered as “indicative of decreased cell viability” and “indicative of unchanged and increased viability” because the claim does not recite such.
As to claim 58 it is unclear which the growing and/or transferring is required to performed “under conditions sufficient to grow at least one axon” and what are such conditions because the claim does not recite such.
As to claim 58, it is unclear which/what neural tissue is being referenced by “the neural tissue” because the claim previously recites “growing neural tissue” and “transferring neural tissue”. The neural tissue recited in each phrase/alternative is not required to be the same. It is noted that the measuring and quantifying can be done visually and/or mentally. Furthermore, it is unclear what is required to be done for the quantifying to be based upon the compound action potential because the claim does not clearly recite such.
Claim 58 recites the limitation "the levels of myelination of the neural tissue" in the last paragraph. There is insufficient antecedent basis for this limitation in the claim.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-4, 14, 16-18, 20-21, 29-30, and 37 is/are rejected under 35 U.S.C. 102(a)(1),(a)(2) as being anticipated by Fang et al., US 2011/0125001.
Fang discloses a three-dimensional microelectrode array (3D microelectrode array 30; abstract; figure 5C; paragraphs (0020, 00291) comprising: a chip that further comprises at least one two-dimensional electrode, at least one three-dimensional electrode, or a combination thereof (a carrier chip 40 comprising 2D microelectrode array 10 and 3D microelectrode structure 1; figure 5C; paragraphs [0020, 0027, 0032]); wherein the three-dimensional microelectrode array is configured to provide real-time, reliable detection of one or more bioelectrical signals in a microengineered physiological system (3D microelectrode array 1 is configured to perform measurement of biological tissues including neural prostheses comprising neuronal cells; abstract; paragraphs (0002, 0034-0036)).
As to claim 2, Fang discloses the three-dimensional microelectrode array of claim 1. Fang further discloses wherein the one or more bioelectrical signals comprise single action potentials, compound action potentials, high frequency waves, low frequency waves, or a combination thereof (measuring action potentials including single action potentials; abstract; paragraphs (0002, 0035-0036)).
As to claims 3-4, 14, and 37 the microengineered physiological system is not a structural element of the invention.
As to claim 16, Fang discloses the three-dimensional microelectrode array of claim 1. Fang further discloses wherein the three-dimensional microelectrode array comprises a biocompatible conductive ink, a biocompatible conductive paste, a biocompatible conductive composite, or a combination thereof (the 3D microelectrode structure 1 including 3D microelectrode array 30 comprises a biocompatible conductive paste defined by silver conductive paste; figure 5C; paragraphs [0020, 0032, 0036]).
As to claim 17, Fang discloses the three-dimensional microelectrode array of claim 1. Fang further discloses wherein the three-dimensional microelectrode array further comprises one or more vias (the 3D microelectrode structure 1 including 3D microelectrode array 30 comprises one or more vias as shown; figure 5C).
As to claim 18, Fang discloses the three-dimensional microelectrode array of claim 1. Fang further discloses comprising an insulation layer (an insulation film 400, figure 3B; paragraphs [0020, 0027J). Fang further discloses wherein the insulation layer comprises a material that is biocompatible (insulating film 400 comprises a biocompatible material such as silicon dioxide; paragraphs [0020, 0027)).
As to claim 20, Fang discloses the three-dimensional microelectrode array of claim 18. Fang further discloses wherein the insulation layer comprises parylene, poly-di-methyl-siloxane (PDMS). SU-8, silicon dioxide, polyimide, polyurethane, poly lactic acid, poly glycolic acid, poly lactic glycolic acid, poly vinyl alcohol, polystyrene, poly ethylene glycol, poly ethylene terephthalate, poly ethylene terephthalate glycol, poly ethylene naphthalate, or a combination thereof (insulating film 400 comprises silicon dioxide; paragraph [0027)).
As to claim 21, Fang discloses the three-dimensional microelectrode array of claim 1. Fang further discloses comprising volumetric stimulators configured to stimulate the microengineered physiological system (volumetric stimulators defined by probe 12 comprising electrodes 120 configured to stimulate biological tissues including neural prostheses comprising neuronal cells; abstract; paragraphs {0002, 0035-0036]).
Fang discloses the three-dimensional microelectrode array of claim 1. Fang further discloses wherein the microelectrode array is comprised of a biocompatible material (3D microelectrode 30 being stacked 2D microelectrode arrays 10 comprising biocompatible material; figure 5C; paragraphs (0020, 00261).
As to claim 29, Fang discloses the three-dimensional microelectrode array of claim 28. Fang further discloses wherein the three-dimensional microelectrode array are configured to maintain viability of neuronal cells (the 3D microelectrode structure 1 including 3D microelectrode array 30 is configured to measure biological tissue and comprises biocompatible material, thereby configured to maintain viability of neuronal cells; abstract; paragraphs [0020, 0034-0036]).
As per claim 30, the microengineered physiological system is not an element of the invention. Fang further discloses wherein the microengineered physiological system comprises at least one neuronal cell with a structure analogous to peripheral nerve anatomy (the biological tissue including cortices comprising neuronal cells is a structure analogous to peripheral nerve anatomy; abstract; paragraphs [0034-0036]).
As per claim 31, Fang discloses the three-dimensional microelectrode array of claim 1. Fang further discloses wherein the three-dimensional microelectrodes comprise microneedle-type electrodes (the 3D microelectrode structure 1 including 3D microelectrode array 30 comprise microneedle-type electrodes as shown; figure 5C).
Claim(s) 1-4, 14, and 37 is/are rejected under 35 U.S.C. 102(a)(1),(a)(2) as being anticipated by Allen, M et al., US 2013/0306356.
Allen discloses a three-dimensional microelectrode array (a three -dimensional microelectrode array defined by three-dimensional conductive structures fabricated in an array; paragraph (00561) comprising: a chip that further comprises at least one two-dimensional electrode, at least one three-dimensional electrode, or a combination thereof (the three-dimensional conductive structures are supported on a substrate (chip) comprising at least one three-dimensional conductive structure; figure 2A; paragraphs [0054-0056]); wherein the three-dimensional microelectrode array is configured to provide real-time, reliable detection of one or more bioelectrical signals in a microengineered physiological system (the three-dimensional structures configured as a microneedle array for detecting bioelectric signals when performing electroporation for testing drug delivery to in-vitro cultivated cells (microengineered physiological system); paragraphs (0003, 0064, 0083]).
As to claims 3-4, 14, and 37 the microengineered physiological system is not a structural element of the invention.
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.
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.
Claim(s) 6, 8-9, 13-14, and 50-58 is/are rejected under 35 U.S.C. 103 as being unpatentable over Allen et al. as applied above, and further in view of Curley et al., US 2017/0276668.
Allen fails to disclose wherein the neural architecture comprises an axonal growth region, a ganglion region, a dendritic region, a synaptic region, a spheroid region, or a combination thereof.
Curley further discloses wherein the neural architecture comprises an axonal growth region, a ganglion region, a dendritic region, a synaptic region, a spheroid region, or a combination thereof (the micropatterned hydrogel comprises an axonal growth region as shown; figures 5A-6C, 24; paragraphs (0043, 0184]).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the in-vitro cells of Allen, to provide wherein the neural architecture comprises an axonal growth region, a ganglion region, a dendritic region, a synaptic region, a spheroid region, or a combination thereof, as taught by Curley, in order to provide the advantage of using micropatterned hydrogels being a material that is easy to produce, low cost and biocompatible to support axon growth when using the hydrogels for neuronal cell cultivation.
As to claim 6, Allen fails to explicitly disclose comprising a first plurality of electrodes positioned in the ganglion region or spheroid region and a second plurality of electrodes positioned at defined intervals down the axonal growth region.
Curley further discloses comprising a first plurality of electrodes positioned in the ganglion region or spheroid region (a first plurality of electrode defined by recording electrodes positioned in the ganglion position; figures 8A, 24; paragraphs (0044, 0093, 01551) and a second plurality of electrodes positioned at defined intervals down the axonal growth region (a second plurality of electrodes defined by a plurality of electrodes/stimulating electrodes positioned at defined intervals down the axonal growth region as shown; figures 8A, 24; paragraphs (0044, 0093, 0122]).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide comprising a first plurality of electrodes positioned in the ganglion region or spheroid region and a second plurality of electrodes positioned at defined intervals down the axonal growth region, as taught by Curley, in order to provide the advantage of a simultaneous electrical stimulation and electrical measurement to capture a real-time measurement to accurately observe how cultivated neuronal cells behave by using multiple electrodes positioned along different regions of the neuronal cells.
As to claim 8, Allen in view of Curley fails to disclose wherein the first plurality of electrodes comprises at least one planar electrode, the second plurality of electrodes comprises at least one three-dimensional electrode, or vice versa.
However, it would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the electrodes of Curley, to explicitly provide wherein the first plurality of electrodes comprises at least one planar electrode, the second plurality of electrodes comprises at least one three-dimensional electrode, or vice versa, in order to provide the advantage of using planar electrodes as recording electrodes and using a three-dimensional microelectrode array as the stimulating electrodes to simultaneously stimulate and record multiple points, thereby ensuring an high sensitivity of measurement captured in real-tune.
As to claim 9, Allen fails to disclose wherein the defined intervals comprise up to about 5mm intervals.
Curley further discloses wherein the defined intervals comprise up to about 5mm intervals (the defined intervals of the stimulating electrodes positioned along the tract shown in figure 24, may comprise being positioned 2.25 mm from the ganglion and the growth of the neuron cells have a length of 5mm; figure 24; paragraph (0235]). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide wherein the defined intervals comprise up to about 5mm intervals, as taught by Curley, in order to provide the advantage of improving electrical stimulation along the full length of the neuronal cells to capture real-time behaviors of neuronal cells.
As to claim 13, Allen fails to disclose wherein the three-dimensional microelectrode array is configured to detect one or more bioelectric signals of at least 10 µV.
Curley further discloses wherein the three-dimensional microelectrode array is configured to detect one or more bioelectric signals of at least 10 µV (action potentials detected at a signal greater than 0 µV between 20 µV as shown; figure 10D; paragraph (0095]).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the detection of Allen, to provide wherein the three-dimensional microelectrode array is configured to detect one or more bioelectric signals of at least 10 µV, as taught by Curley, in order to provide the advantages of cultivating neuronal cells and using electrodes sensitive to detect action potentials of the neuronal cell being a small signal of at least 10 µV.
As to claim 14, Allen further discloses the three-dimensional microelectrode array (three-dimensional conductive structures fabricated in an array; paragraph [0056]). Allen fails to disclose wherein the three-dimensional microelectrode array is configured to detect one or more bioelectric signals in a microengineered physiological system for up to one year.
Curley further discloses wherein the electrodes are configured to detect one or more bioe1ectric signals in a microengineered physiological system for up to one year (the electrodes shown in figure 24, are configured to detect signals in the cell culturing system having grown neuronal culls from a period of about 1 day to about 1 year; abstract; figure 24; paragraphs
[0014, 00511).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide wherein the three-dimensional microelectrode array is configured to detect one or more bioelectric signals in a microengineered physiological system for up to one year, as taught by Curley in order to provide the advantage of improving length of time of detection by measuring electrical signals while growing cells from a period of 1 day to 1 year, thereby giving a more detailed account as to understanding neuronal cells behaviors over time.
Curley further discloses is configured to measure compound action potentials for an inference of conduction velocity, amplitude, integral, excitability after compound administration, threshold, sensitivity, CAP time width, CAP waveform shape, or a combination thereof (the cell cultivating system measured for compound action potential for an inference of amplitude; abstract; figures 88-8C; paragraphs [0061, 00931). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide is configured to measure compound action potentials for an inference of conduction velocity, amplitude, integral, excitability after compound administration, threshold, sensitivity, CAP time width, CAP waveform shape, or a combination thereof, as taught by Curley, in order to provide the advantage of using a signal associated with neuronal cells that is easily detected using a microelectrode array.
Claim(s) 22, 32, and 41-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Allen et al. as applied above, and further in view of ROSS, J. et al., US 2010/0120626.
As to claim 22, Allen discloses the three-dimensional microelectrode array of claim 1. Allen fails to disclose wherein the electrodes comprise a diameter of about 50 µm or less. Ross further discloses wherein the electrodes comprise a diameter of about 50 µm or less (the microelectrodes having a diameter of about 1 to about 500 microns; paragraph [0046]).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide wherein the electrodes comprise a diameter of about 50 µm or less, as taught by Ross, in order to provide the advantage of using a micron sized electrodes sensitive and small enough to effectively detect bioelectric signals in nerve cells.
Ross further discloses wherein the electrodes comprise a diameter of about up to about 1000 µm (the microelectrodes having a diameter of about 1 mm which is the same as 1000 microns; paragraph [00461).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide wherein the electrodes comprise a diameter of about 1000 µm or less, as taught by Ross, in order to provide the advantage of using a micron sized electrodes sensitive and small enough to effectively detect bioelectric signals in nerve cells.
Ross further discloses wherein the electrodes comprise a diameter of about 30 µm or less (the microelectrodes having a diameter of about 1 to about 500 microns; paragraph [0046]). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide wherein the electrodes comprise a diameter of about 30 µm or less, as taught by Ross, in order to provide the advantage of using a micron sized electrodes sensitive and small enough to effectively detect bioelectric signals in nerve cells.
Ross further discloses wherein the electrodes comprise a diameter of about 30-50 µm (the microelectrodes having a diameter of about 1 to about 500 microns; paragraph [0046]). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide wherein the electrodes comprise a diameter of about 30-50 µm or less, as taught by Ross, in order to provide the advantage of using a micron sized electrodes sensitive and small enough to effectively detect bioelectric signals in nerve cells.
As to claim 32, Allen fails to disclose wherein the at least one three-dimensional electrode comprises a height up to about 1000µm.
Ross further discloses wherein the at least one three-dimensional electrode comprises a height up to about 1000 µm (the microelectrodes having a length being height of about 500 microns; paragraph [0047]).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide wherein the at least one three-dimensional electrode comprises a height up to about 1000 µm, as taught by Ross, in order to provide the advantage of using a micron sized electrodes sensitive and long enough to effectively detect bioelectric signals in nerve cells in microfluidic channels.
Ross further discloses wherein the at least one three-dimensional electrode comprises a height of between about 300 µm to about 1000 µm (the microelectrodes having a length being height of 1 to about 500 microns; paragraph [0047]). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide wherein the at least one three-dimensional electrode comprises a height of between about 300 µm to about 1000µm, as taught by Ross, in order to provide the advantage of using a micron sized electrodes sensitive and long enough to effectively detect bioelectric signals in nerve cells in microfluidic channels.
Ross further discloses wherein the at least one three-dimensional electrode comprises a height of up to about 150 µm (the microelectrodes having a length being height of 1 to about 500 microns; paragraph [0047]). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide wherein the at least one three-dimensional electrode comprises a height of up to about 150 µm, as taught by Ross, in order to provide the advantage of using a micron sized electrodes sensitive and long enough to effectively detect bioelectric signals in nerve cells in microfluidic channels.
Ross further discloses wherein the at least one three-dimensional electrode comprises a height of between about 50 µm to about 150 µm (the microelectrodes having a length being height of 1 to about 500 microns; paragraph [0047]). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the device of Allen, to provide wherein the at least one three-dimensional electrode comprises a height of between about 50 µm to about 150 µm, as taught by Ross, in order to provide the advantage of using a micron sized electrodes sensitive and long enough to effectively detect bioelectric signals in nerve cells in microfluidic channels.
As to claim 41, Allen further discloses the three-dimensional microelectrode array (three-dimensional conductive structures fabricated in an array; paragraph [0056]). Allen fails to disclose wherein the three-dimensional microelectrode array comprises a conductive trace layer, a polyethylene terephthalate insulation layer, micro-towers, or a combination thereof. Ross further discloses wherein the three-dimensional microelectrode array comprises a conductive trace layer, a polyethylene terephthalate insulation layer, micro-towers, or a combination thereof (the microelectrode array MEA comprises a layer including metal traces; figure 4A; paragraphs [0023, 0028}). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the conductive structures of Allen, to provide wherein the three-dimensional microelectrode array comprises a conductive trace layer, a polyethylene terephthalate insulation layer, micro-towers, or a combination thereof, as taught by Ross, in order to provide the advantages of providing a distinctive electrical pathway to ensure electrical signals are effectively supplied directly to the microelectrodes.
As to claim 42, Allen fails to disclose wherein the at least one micro-tower is coated with micro-porous platinum, nano-porous platinum, nano-gold, or a combination thereof. However it would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the microelectrode structures of Ross, to provide wherein the at least one micro-tower is coated with micro-porous platinum, nano-porous platinum, nano-gold, or a combination thereof, in order to provide the advantage of improving sensitivity of the electrodes comprising of micro-towers by coating the micro-towers with an high conducting conductor.
As to claim 43, Allen further discloses the three-dimensional microelectrode array (three-dimensional conductive structures fabricated in an array; paragraph [0056]). Allen fails to disclose wherein the three-dimensional microelectrode array comprises a titanium/gold metal trace. Ross further discloses wherein the three-dimensional microelectrode array comprises a titanium/gold metal trace (the microelectrode array MEA comprises titanium for adhesion and gold for metal traces; paragraph [0023]). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the conductive structures of Allen, to provide wherein the three-dimensional microelectrode array comprises a titanium/gold metal trace, as taught by Ross, in order to provide the advantages of providing a distinctive electrical pathway to ensure electrical signals are effectively supplied directly to the microelectrodes.
Claim(s) 43 is/are rejected under 35 U.S.C. 103 as being unpatentable over Allen et al. in view of Ross as applied to claims 22, 32, and 41-42 above, and further in view of Fang et al., US 2011/0125001.
Fang discloses the three-dimensional microelectrode array comprises a trace layer (the 3D microstructure 1 including the 3D microelectrode array comprises a trace layer as shown; figure 5C; paragraph [00201) and a silicon dioxide insulation layer (insulating film 400 comprises silicon dioxide; paragraph
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the traces of Fang, to modified teachings of Allen, in order to provide the advantages of providing a distinctive electrical pathway to ensure electrical signals are effectively supplied directly to the microelectrodes by using a high conductive material for the traces forming the electrical pathway.
Claim(s) 45 and 47-49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Curley et al., US 2017/0276668 as applied above, and further in view of Allen, M et al., US 2013/0306356 as applied above.
As to claim 45, Curley discloses a system for reproducibly detecting compound action potentials in microengineered physiological system (a three-dimensional cell culturing system/cell culturing system measures for a compound action potential; abstract; paragraph [0234]), the system comprising an