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 .
Introductory Note
Applicants reply filed 1/23/2026 is acknowledged.
In response to the Notice of Non-Complaint Amendment dated 12/9/2025, Applicants filed claim amendments and a reply on 1/23/2026.
The Notice indicated that claim amendments filed 8/25/2025 was non-complaint because it was not responsive to the prior Office action. While the original claims examined in the prior office action were directed to an animal model, specifically a model comprising a kindled animal brain wherein the model has an intended use for the analysis of events associated with brain seizures and could be stimulated (“upon stimulation”) to provide for seizure-associated neural events that can be analyzed by electrophysiology and MRI, the amended claimed filed 8/25/2025 were directed to a method of generating a model for the analysis of events associated with brain seizures wherein the method comprised receiving electrophysiology and MRI data collected from a kindled animal brain, and analyzing said data.
In response to the Notice, claim amendments filed 1/23/2026 now again recite “A model for the analysis of events associated with brain seizures” but now the model comprises electrophysiology and MRI data collected from a kindled animal brain and a “map of a network associated with the at least one neural event”.
In the reply filed along with the most recent claim amendments (1/23/2026), Applicant states that “Claims 4-22 and 24-25 have been amended to replace "system" with "method" and for the sake of clarity.” (page 7, para 5). This statement seems to have copied inadvertently from the previous response (8/25/2025) since claims are now amended back to recite “a model” in place of “a method”.
This issue is also noted in the responses to rejections of record. For example, in response to the U.S.C. 112b rejections of record, Applicant states “However, amended claim 1 does not claim both an apparatus and method but rather specifically refers to a model containing data associated with a kindled animal brain, which does not involve active steps.” but then retains the statement from the previous response (8/25/2025) “Applicant submits that active steps are clear in view of a claim directed to a method.” (emphasis added; page 8, para 2).
However in response to the U.S.C. 101 rejection of record, Applicant clearly states “amended claim 1, the independent claim to which claims 6, 7, 9, 13, and 16 depend on, is directed to a model containing data associated with a kindled animal brain. Applicant submits that amended claim 1 is directed to a product” (emphasis added; page 9, para 2).
Thus, it is clear on the record, that the instant claims are product claims comprising data generated from the kindled animal brain (i.e. the originally claimed product) and a map of a network associated with the at least one neural event.
Claims status
Claims 1-4, 6, 7, 9, 13, 16, 19, 20 and 22, 26-27 and 31-36 is/are currently pending and is/are under examination.
Claim Objections
Claim 1 is objected to because of the following informalities:
(i) Line 23 is missing a punctuation to separate the two wherein clauses.
(ii) The “and” at the end of line 10 should be removed. When listing more than two elements comprised in a claimed product, “and” should be used before the last element only. In the instant case, the last element of the claimed model is “a map of a network […]” that is already preceded with an “and”.
Appropriate corrections are required.
Claim 22 is objected to because of the following informalities: Claim has several grammatical issues such as excess articles, verbs and missing proper prepositions. Following language is recommended: “a binarized s based on a percent of the voxels . Appropriate correction is required.
Claim 26 is objected to because of the following informalities:
(i) Claim recites “therapeutic invention” in line 5. This appears to be a spelling error. Following language is recommended: “therapeutic intervention”.
(ii) Claim recites “the model generated by the model of claim 1” in line 4. This appears to be circular phrasing. Following language is recommended: “the
Appropriate corrections are required.
Claim 36 is objected to because of the following informalities: Claim incorrectly recites “than” in place of “that”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Previous rejections of Claims 1-4, 6, 7, 9, 13, 16, 19, and 22 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 is withdrawn in light of claim amendments.
Claim 20 was not amended to overcome the previous 112b rejection and amendments to other claims introduce new indefiniteness issues addressed below.
Claim 20 remains and Claims 1-4, 6, 7, 9, 13, 16, 19, 22, 26-27 and 31-36 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.
Claim 1 recites “the activation volumes” in line 14. There is insufficient antecedent basis for this limitation in the claim. For the purpose of compact prosecution, the claim(s) 1 is/are interpreted as “wherein the subset of MRI data of the plurality of individual regions comprises quantification of activation volumes for the individual regions and individual regions of the plurality of regions having the largest activation volumes based on quantified activation volumes”.
Claim 2 recites “The model of claim 1, further comprises a neural event propagation based on analyzing the MRI data”. The phrase “neural event propagation” in the context of this claim which is directed to a product of claim 1 is unclear. The specification teaches that the disclosed method that combines electrophysiological technique measuring local field potentials with fMRI allows for imaging of seizure propagation to identify the propagation pattern [0012], [0013], [0059], [0065], [00130]. For the purpose of compact prosecution, the claim(s) 2 is/are interpreted as “The model of claim 1, further comprises a neural event propagation pattern data based on analyzing the MRI data”.
Claim 19 recites “The model of claim 1, further comprising migrating seizure core”. The model of claim 1 is a product comprising data. It is unclear how a product could comprise a seizure, including a migrating seizure or its core. The specification teaches that the disclosed method that combines electrophysiological technique measuring local field potentials with fMRI allows for identification of the core of a migrating seizure upon imaging of individual seizure events [0014], [0059], [0063], [0101], [00138]. For the purpose of compact prosecution, the claim(s) 19 is/are interpreted to require data generated from a plurality of neural events wherein the plurality of neural events are associated with a migrating seizure.
Claim 20 recites “a seizure inset zone”. Neither the claim nor the specification provides any guidance regarding this term and this term is not known in the art. The specification teaches a “seizure onset zone” in [0055]. For the purpose of compact prosecution, claim 20 is interpreted as “a seizure onset zone”.
Claim 20 also recites “The model of claim 19, further comprising a seizure inset zone”. The model of claim 19 is a product comprising data. It is unclear how a product could comprise a seizure, including its onset zone. For the purpose of compact prosecution, the claim(s) 20 is/are interpreted as “The model of claim 19, further comprising a single- photon emission computed tomography (SPECT) data for identification of seizure inset zone (SOZ) localized based on the migrating seizure core
Claim 26 is directed to a method for “developing a therapeutic intervention” wherein the method comprises determining the effect of a therapeutic intervention on neural events by applying the therapeutic intervention to the model of claim 1. The applied therapeutic interventions are listed in the claim. The model of claim 1 is a product comprising data. It is unclear how the therapeutic interventions of claim 26 could be applied to the model of claim 1. For the purpose of compact prosecution, the claim(s) 26 is/are interpreted as “determining the effect of the therapeutic intervention on neural events reflecting functional and neural circuit using the model of claim 1, wherein the therapeutic intervention is applied to the brain” .
Claim 27 appears to recite the same limitation as claim 26 that it depends from, except it uses a present tense as compared to the past tense in claim 26. It is unclear how the present/past tense effects the method that comprises a single step of determining the effect of the therapeutic intervention that is already administered.
Claim 36 includes “connectivity data” which appears to be “conditional probability” data which appears to show if a brain region is active during the neural event. Figure 2 shows that kindling increased connectivity between two brain regions however the data used for this conclusion is MRI data from before [126]. In [00161], the specification states that “For the 10 Hz hippocampal connectivity data, single subject voxel level maps were generated using the aforementioned procedure and thresholded at P<0.001.” Thus, again, it appears that “connectivity data” is voxel-based MRI data. Furthermore, conditional probability requires a comparison of two events, generally calculating a probability of an event occurring if another event has already occurred. In the instant case, it is unclear what the two comparative events are. Even if it is interpreted that the two events are baseline and stimulus, it is unclear how calculating the probability of a region being active during stimulus if baseline has occurred could provide a connectivity data. For the purpose of compact prosecution, the claim(s) 36 is/are interpreted as data that shows if a brain region is active during the neural event.
Claims 2-4, 6, 7, 9, 13, 16, 19, 20 and 22, 26-27 and 31-36 is/are rejected due their dependence on claim 1 because they do not clarify the 112b issue noted with claim 1.
Claims 3, 9 is/are rejected due their dependence on claim 2 because they do not clarify the 112b issue noted with claim 2.
Claim 20 is/are rejected due their dependence on claim 19 because they do not clarify the 112b issue noted with claim 19.
Claims 27, 31-35 is/are rejected due their dependence on claim 26 because they do not clarify the 112b issue noted with claim 26.
Claim Interpretation
Generally, when the claims are indefinite, vague or unclear, they cannot be construed without speculation or conjecture; therefore, the indefinite claims are not treated on the merits with respect to prior art. See In re Steele, 305 F.2d 859, 862 (CCPA 1962) (A prior art rejection cannot be sustained if the hypothetical person of ordinary skill in the art would have to make speculative assumptions concerning the meaning of claim language.); see also In re Wilson, 424 F.2d 1382, 1385 (CCPA 1970) ("If no reasonably definite meaning can be ascribed to certain terms in the claim, the subject matter does not become obvious-the claim becomes indefinite."). Notwithstanding Steele, the Office has made every attempt to construe the claims in what the Office believes is the intent of the Applicants in the interest of compact prosecution.
In addition to the claim interpretations presented for the purpose of compact prosecution in the U.S.C. 112b rejection of the claims above, additional claim interpretations are presented below:
Bases on Applicants reply filed 1/23/2026, claim 1 is directed to a model containing data associated with a kindled animal brain. and that the model of claim 1 is directed to a product” (page 9, para 2). Specifically, the model of claim 1 comprises the following:
(i) normalized band power data generated using electrophysiological methods, wherein the normalized band power data is data generated during stimulation divided by baseline data generated pre-stimulation (See limitation “a band power of electrophysiology data calculated during a stimulation divided by a band power prior to the stimulation”),
(ii) activation volume data generated using MRI, wherein the activation volume data is from a plurality of brain regions, including brain regions that had the largest activation volumes (See limitation “magnetic resonance imaging (MRI) data comprising a subset of MRI data segmented into a plurality of individual regions, wherein the subset of MRI data of the plurality of individual regions comprises individual regions of the plurality of regions having the largest activation volumes based on quantification of the activation volumes”), and
(iii) a map of a network associated with the at least one neural event based on the MRI data, the electrophysiology data, or a combination thereof;
wherein the data of (i) and (ii) are generated simultaneously from at least one neural event produced in response to a stimulation of a kindled animal brain (See limitations “wherein the subset of MRI data and the band power are indicative of at least one neural event,, wherein the MRI data and the electrophysiology data was simultaneously collected from a kindled animal brain wherein the electrophysiology data, the MRI data, or both includes data of the at least one neural event reflecting functional and neural circuit changes, wherein the at least one neural event was responsive to the stimulation of the brain).
Regarding data (band power and activation volume) from the neural event produced in response to a stimulation of a kindled animal brain, following interpretation is provided: The claimed product comprises data. The structure of these claimed data is limited to the data generated from a neural event. Establishing the features of the said neural event is important to construe claim 1.
Claim 1 recites that the neural event reflects functional and circuit level changes.
It also a recites a “product-by-process limitation”, reciting that the neural event is in response to any stimulation to a kindled animal brain. According to MPEP 2113, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.”. Following discussion is to determine if the recited product-by-process limitation provides a structure to the data, if any.
Type of stimulation affects the features of the neural event and the data generated from it. At least , claims 6 and 19 recite that the neural event could be a type of seizure event (FBTC, migrating seizure). However, this would depend on at least the type, the intensity/frequency and the location of the stimulation. For example, see limitation in claim 7 that is directed to electrical/optogenetic stimulation type. See limitation in claim 13 that is directed to a sub-threshold intensity of stimulation that would not result in a seizure or claim 6 that recites “changed” in excitatory ventral hippocampal network. Claim 1 does not require the generated neural event to be a specific type of neural event or in response to any specific type (natural or artificial), intensity/frequency or location of stimulation. Although the claim recites that the neural event is in response to stimulation of a kindled animal brain, there is no evidence of record that neural events in kindled animal brain are always distinct from neural events in a non-kindled brain such that data generated from a neural event in a kindled animal brain is inherently different from data generated from a neural event in a non-kindled animal brain. Thus, the product-by-process limitation (collected from kindled animal brain) does not appear to provide any specific structure to the claimed data.
Taken together, the claimed model is broadly interpreted to comprise data from a neural event that reflects functional and circuit level changes.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Rejection of Claims 1-4, 6, 7, 13, 16, 19, 20 and 22 under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism is withdrawn in light of claim amendment.
Rejection of Claims 6, 7, 9, 13 and 16 under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter, specifically falling under “Use” claims (see MPEP 2173.05q) is withdrawn in light of claim amendments.
Claims 1-4, 6, 7, 9, 13, 16, 19, 20 and 22, 26-27 and 31-36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Subject Matter Eligibility Guidance:
A three-part inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101 for process claims that involve laws of nature. See Subject Matter Eligibility Guidance, MPEP § 2106. This inquiry comprises answering: 1) Is the claimed invention directed to one of the four statutory patent-eligible subject matter categories: process, machine, manufacture, or composition of matter? 2A) Does the claim recite or involve one or more judicial exceptions? Judicial exceptions include abstract ideas, laws of nature/natural principles, natural phenomena, and natural products. 2B) Does the claim as a whole recite something significantly more than the judicial exception(s)?
Claim Interpretation: With respect to claims 1-4, 6, 7, 9, 13, 16, 19, 20, 22 and, 36 Applicant's invention is interpreted as a model that comprises data (Electrophysiology and MRI) generated from an animal brain during a neural event and a map generated from said data. Further, the data recited in the claims is mathematically transformed data (see limitations pertaining to calculation of band power, quantification of activation volumes, calculation of mean time course in the claims). Additionally the data represents the naturally occurring relationship between neural activity and its electrophysiological or blood flow (as measured by MRI) properties.
Claims 26, 27, 31-35 are directed to a method of using the model of claim 1 comprising mental processes such as determining the effect of known therapeutic intervention on neural events.
Analysis in View of Claim Interpretation and Subject Matter Eligibility Guidance:
1) Statutory Subject Matter: Claims 1-4, 6, 7, 9, 13, 16, 19, 20, 22 and, 36 are directed to a model, which is a product. Therefore, claims 1-4, 6, 7, 9, 13, 16, 19, 20, 22 and, 36 are directed to statutory subject matter.
Of note, as noted in MPEP 2106.03, data alone is not directed to any statutory category, especially product which require a physical and tangible form. However, in the instant case, the claims also comprise a map generated based on the data which is expected to have a physical form.
Claims 26, 27, 31-35 are directed to a method, which is a process. Therefore, claims 26, 27, 31-35 are directed to statutory subject matter.
2A) Judicial Exception:
(Prong One) Does the claim recite a judicial exception? Claims 1-4, 6, 7, 9, 13, 16, 19, 20, 22 and, 36 recite a judicial exception because they recite mathematical calculations as well as natural phenomenon. Claims recite limitations such as “a band power of electrophysiology data calculated during a stimulation divided by a band power prior to the stimulation”, “the plurality of regions having the largest activation volumes based on quantification of the activation volumes”, “analyzing the MRI data, the analyzing comprising: low pass filtering the MRI data; registering the MRI data to a brain atlas; segmenting the MRI data into a plurality of individual regions based on the registering; and calculating a mean time course for a plurality of voxels in an individual region of the plurality of individual regions”, “calculating the mean time course comprises determining a time at which a signal reached four standard deviations from a baseline”, “a voxel based on a percent the voxel was activated during a portion of an induction period”. These are reciting mathematical calculations, which are Abstract Ideas.
Further, claims encompass natural phenomenon because they are directed to the naturally occurring relationship between neural activity and its electrophysiological or blood flow (as measured by MRI) properties.
Claims 26, 27, 31-35 recite a judicial exception because they recite mental processes. Claims recite limitations such as “determining the effect on neural events reflecting functional and neural circuit changes obtained by applying a therapeutic intervention to the model generated by the model of claim 1”.
(Prong Two) Does the claim recite additional elements that integrate the judicial exception into a practical application? Claims 1-4, 6, 7, 9, 13, 16, 19, 20, 22 and, 36 do not recite additional elements that integrate the judicial exception into a practical application because the only additional element recited is directed to generating a map of neural network activity from the data which is also expected to require mathematical calculations. Other additional elements are directed to the type of neural activity measured to generate the data using mathematical calculations (claims 6, 7, 19, 20) and means to electrically invoke the neural activity (claims 4, 7, 13, 16).
These limitations are not indicative of integrating the judicial exceptions into practical applications, such as in MPEP 2106.04d. Critically, the additional elements amount to adding insignificant extra-solution activities that were routine in the art. Generating neural activity maps from electrophysiological and MRI data wherein the neural activity, such as seizures, was electrically invoked was already well-known in the art. See for examples Fang et al (Journal of Neuroscience Methods 218 (2013) 184– 195), Duffy et al (NeuroImage 123 (2015) 173–184), Lee 2015 (US 2015/0366482 A1, Dec. 24, 2015; IDS 8/25/2025) and Lee et al (US 2018/0199850 A1, July 19, 2018; IDS 8/25/2025) each teaching collecting electrophysiology and MRI data of seizure neural activity evoked by optogenetic electrical stimulation, performing calculations such as claimed and generating neural activity maps.
Claims 26, 27, 31-35 do not recite additional elements that integrate the judicial exception into a practical application because the only additional elements are directed to applying the judicial exception to different types of neural activities or generic therapeutics. These limitations are not indicative of integrating the judicial exceptions into practical applications because these amount to nothing more than “apply it”. The additional limitations are a generic therapeutic, such as a generic pharmaceutical or surgery, DBS etc. that are common in treatment of seizures or seizure-associated comorbidities or application of the judicial exception to different types of seizures. Such applications of using electrophysiology and MRI data of seizure neural activity to assess therapeutic efficacy was well-known. See Lee 2015 and Lee. The specification does not disclose any example where any therapeutic was applied. These additional limitations do not have sufficient particularity such that it could be understood that the judicial exception is integrated into a particular treatment or prophylaxis (see MPEP 2106.04(d)(2).
2B) Significantly More: The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements were well-understood, routine and conventional such that they could not contribute an inventive concept to the claims. As noted above, collection of electrophysiology and MRI data of seizure neural activity evoked by optogenetic electrical stimulation, performing calculations such as claimed and generating neural activity maps had been routinely done in the art. Furthermore, application of such data and map generated from such data to evaluate therapeutics had also been contemplated.
Summary: On balance the relevant factors weigh against eligibility and claims do not qualify as eligible subject matter under 35 U.S.C. § 101.
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.
Rejection of Claim(s) 1-4, 6, 7, 9, 13, 16, 19, 20 and 22 under 35 U.S.C. 102(a)(1) as being anticipated by Osawa et al (Optogenetically Induced Seizure and the Longitudinal Hippocampal Network Dynamics. PLOS One, Vol. 8, Issue 4, April 2013) is withdrawn in light of claim amendment. Osawa taught an kindled animal brain and generating electrophysiological data from it. However Osawa did not teach MRI data.
Rejection of Claim(s) 1-4, 6, 7, 9, 13, 16, 19, 20 and 22 under 35 U.S.C. 102(a)(1) as being anticipates by Cela et al (An Optogenetic Kindling Model of Neocortical Epilepsy; Scientific Reports, 9:5236; Published online March 27, 2019) is withdrawn in light of claim amendment. Cela taught an kindled animal brain and generating electrophysiological data from it. However Cela did not teach MRI data.
Claim(s) 1, 2, 4, 6, 7, 9, 13, 16, 19, 22, 26, 27, 31-36 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al (US 2018/0199850 A1; July 19, 2018; IDS 8/25/2025) as evidenced by Kung et al (Basics of BOLD activities” and “Data Preprocessing” in fMRI, Handout for a talk at NCKU MRI center, July 7, 2015).
Regarding claim 1, Lee teaches methods that comprise monitoring brain activity using simultaneous electrophysiology and MRI technique [0018, 0019, 0068, 0069, 0154]. This method is used to analyze and model events associated with brain seizures (Figures 3, 4). Lee’s model comprises (i) normalized band power data generated using electrophysiological methods, wherein the normalized band power data is data generated during stimulation divided by baseline data generated pre-stimulation ([0146], Figure 5e,f; see data normalized to baseline), (ii) activation volume data generated using MRI, wherein the activation volume data is from a plurality of brain regions, including brain regions that had the largest activation volumes ([145, 00154], Figure 4, 5a,b; see MRI bold data showing volumes of activated brain regions), and (iii) a map of a network associated with the at least one neural event based on the MRI data, the electrophysiology data, or a combination thereof ([00145], Figures 3-6 show T-statistic map of network of brain regions activated during the neural event); wherein the data of (i) and (ii) were generated simultaneously from at least one neural event in response to a stimulation that reflects functional and circuit level changes ([00154], Figures 3-6).
Regarding claims 2 and 9, Lee teaches MRI data to generate time course of a neural event propagating (Figure 4h, 5e) wherein the MRI was processed by filtering the MRI data using Gaussian kernel, registering the data to structural images i.e. a brain atlas, segmenting the data to identify individual brain regions ([0140, 0145, 154, 155]). Lee calculates the time course averaged across subjects (= claimed mean time course) for voxels in each region shown ([145, 154], Figure 4h, 5e). Kung evidences that Gaussian filtering has the same effect as low-pass filtering which is performed to remove low frequency noise most seen below 0.1 Hz (slides 35-39). Thus, in teaching a model comprising MRI data filtered by Gaussian kernel, Lee teaches an MRI data that is structurally same as one filtered by a 0.1 Hz low-pass filter.
Regarding claims 4, 6, 7 and 19, Lee teaches an optogenetic electrical stimulation (as required for claims 4, 7; [116, 129, 137, 141, 143], Figure 3) targeted to brain regions of interest, such as intermediate hippocampus (as required by claim 4; [0073]; [0138]) such that the neural event is a FTBC seizure or changes in excitatory network in ventral hippocampus or comprises changes triggered by sub-threshold stimulus or comprises a core of a migrating seizure (as required by claim 6 and 19; see FTBC which is a seizure that spreads from the stimulation spot to bilateral brain regions beyond the localized region in Figures 4-6 and discussed in [0126, 154]; see excitation of ventral hippocampus in Figures 4, 5; see changes triggered by sub-threshold stimulus in Figure 3 and discussed in [154]; see a core of a seizure that migrates from ipsi to septal to contralateral hippocampus in Figure 4h, 5e and discussed [154])
Regarding claims 13, 16, Lee teaches subthreshold and supratheshold stimulation, with respect to seizure induction (Figures 3-5; [0154]).
Regarding claim 22, Lee teaches a map of network of brain regions activated during the neural event that comprises binarized image generated using calculating maximum percent BOLD change in a voxel during stimulation (see Figures 4, 5 for binarized images; see [140, 145] for voxel-based BOLD analysis).
Regarding claims 26 and 27, Lee teaches using their methods and model to evaluate therapeutic treatments such as pharmacological treatment [0115].
Regarding claim 31, 32, 34, 35, Lee teaches that their method can be used to evaluate the following neural events comprising: a FTBC seizure (as required by claims 31, 34) or a core of a migrating seizure (as required by claim 32) or changes in excitatory network in ventral hippocampus (as required by claim 35). See FTBC which is a seizure that spreads from the stimulation spot to bilateral brain regions beyond the localized region in Figures 4-6 and discussed in [0126, 154]; see excitation of ventral hippocampus in Figures 4, 5; see changes triggered by sub-threshold stimulus in Figure 3 and discussed in [154]; see a core of a seizure that migrates from ipsi to septal to contralateral hippocampus in Figure 4h, 5e and discussed [154]).
Regarding claim 33, Lee teaches that their method can be used to evaluate therapeutic treatments for anxiety and cognitive defects, which are epileptic comorbidities [0115].
Regarding claim 36, Lee teaches data that shows if a brain region is active during a neural event (Figures 3-5).
Therefore, Lee anticipates the claimed 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) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee as applied to claims 1, 2 above, as evidenced by Kung et al (Basics of BOLD activities” and “Data Preprocessing” in fMRI, Handout for a talk at NCKU MRI center, July 7, 2015) further in view of Stuart Clare (Functional MRI : Methods and Applications. Thesis, University of Nottingham, October 1997).
The teachings of Lee discussed in U.S.C. 102 rejection of claims 1, 2 above are relied upon for the instant rejection.
Regarding claim 3, Lee uses voxel-wise FDR analysis to identify voxels with significant response in comparison to baseline and represents them as T-statistic map in Figures 3-6 [0145].
Lee does not teach the alternative calculation method of claim 3 wherein a voxel is determined to have a signal i.e. a significant response in comparison to baseline when its signal reaches 4 S.D. from baseline.
Clare teaches that “Many techniques have been proposed for statistically analysing fMRI data, and a variety of these are in general use. The aim of such analysis is to produce an image identifying the regions which show significant signal change in response to the task.” (page 117, para 3). Clare teaches several of these techniques (Chapter 6.3.1-6.3.5). Specifically, the serial statistical tests which results in identification of signal based on statistical significance at a timepoint in comparison to baseline (similar to Lee’s; Section 6.3.4). This method inherently requires generation of a standard deviation map that can also be used to identify voxels with signals significantly different from baseline, such as voxels with signals that are 4 S.D. from baseline (as claimed, page 123, para 3).
Therefore, it would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use a standard deviation map to identify active voxels in place of the T-statistic map of Lee. An ordinary artisan would be motivated to use the standard deviation map in place of Lee’s T-statistic map because it would not require additional statistical analysis. An ordinary artisan would recognize that using a criterion wherein the voxel has signal significantly different from baseline, such as S.D. from baseline (as claimed), would be a simpler approach to identify active voxels.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in
the art at the effective time of filing of the invention, especially in the absence of evidence to the
contrary.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee as applied to claims 1, 19 above, and further in view of Fougere et al (PET and SPECT in epilepsy: A critical review; Epilepsy & Behavior 15 (2009) 50–55).
The teachings of Lee discussed in U.S.C. 102 rejection of claims 1 and 19 above are relied upon for the instant rejection.
Regarding claim 20, Lee teaches the model of claims 1 and 19, comprising data generated from two techniques electrophysiological and MRI, and a network activity map from a neural event that comprises a core of a migrating seizure ([0018, 0019, 0068, 0069, 0154]; see a core of a seizure that migrates from ipsi to septal to contralateral hippocampus in Figure 4h, 5e and discussed [154)
Lee does not teach inclusion of additional data using SPECT that can be used to identify SOZ.
Fougere teaches that SPECT is a well-known technique to identify SOZ in a subject and combination of SPECT with MRI was also known to model multiple epilepsy-related parameters, such as functional imaging, cerebral perfusion, glucose metabolism, morphological abnormalities (Abstract, Introduction para 2). Fougere teaches SPECT data and SOZ identification based on SPECT data (Figure 1).
Therefore, it would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include SOZ identification based on SPECT data, as taught by Fougere, with the electrophysiological and MRI data as taught by Lee. An ordinary artisan would be motivated to include data generated from a third technique, such as SPECT, to more completely analyze and model the neural events using additional SPECT-based parameters. An ordinary artisan would reasonably expect to include data generated from a third technique, such as SPECT, with Lee’s electrophysiological and MRI data because these are three separate data sets that can be each acquired simultaneously or separately. Fougere teaches combination of SPECT with MRI.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in
the art at the effective time of filing of the invention, especially in the absence of evidence to the
contrary.
Response to Arguments
Applicant’s arguments with respect to the U.S.C. 102 rejection of claim(s) have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claim is allowed.
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/MATASHA DHAR/Examiner, Art Unit 1632
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