DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Herein, “the previous Office action” refers to the Non-Final Rejection filed 7/14/2025.
Amendments Received
Amendments to the claims were received on 10/14/2025.
Priority
As detailed on the Filing Receipt filed 5/17/2021, the instant application claims priority to as early as 9/5/2018. At this point in prosecution, all claims are being accorded the earliest claimed priority date.
Claim Status
Claims 8, 14-22 and 24-51 are canceled.
Claims 1-7, 9-13 and 23 are pending.
Claim 13 stands withdraw withdrawn pursuant to 37 CFR 1.142(b) as being directed to a nonelected invention, there being no currently allowable generic or linking claim. Election without traverse was made in the reply filed 4/14/2025.
Claims 1-7, 9-12 and 23 are under examination.
Withdrawn Objections/Rejections
Applicant’s arguments, see pg. 7, para. 4, of the Remarks filed 10/14/2025, with respect to the rejection of claims 23 and 35 under 35 USC § 112(a) have been fully considered and are persuasive. In light of Applicant’s noted amendment of claim 23 to remove terms lacking adequate written description support (e.g., “data acquisition means”) and cancelation of claim 35, the rejection of claims 23 and 35 under 35 USC § 112(a) has been withdrawn.
Applicant’s arguments, see pg. 7, para. 5 – pg. 8, para. 1 of the Remarks filed 10/14/2025, with respect to the rejection of claims 3, 23 and 35 under 35 USC § 112(b) have been fully considered and are persuasive. In light of Applicant’s noted amendment of claims 3 and 23 to define scope of indefinite language (e.g., “only p-values less than the significance level are used”) and cancelation of claim 35, the rejection of claims 3, 23 and 35 under 35 USC § 112(b) has been withdrawn.
In light of Applicant’s cancelation of claims 8 and 35, the rejections of claims 8 and/or 35 under 35 USC §§ 101, 102 and 103 have been withdrawn.
Applicant’s arguments, see pg. 13, para. 5 of the Remarks filed 10/14/2025, with respect to the rejection of claim 35 on grounds of nonstatutory double patenting have been fully considered and are persuasive. In light of Applicant’s noted cancelation of claim 35, the rejection of claim 35 on grounds of nonstatutory double patenting has been withdrawn.
Claim Rejections - 35 USC § 101
35 USC § 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.
Claims 1-7, 9-12 and 23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a natural phenomenon without significantly more (i.e., non-statutory subject matter).
"Claims directed to nothing more than abstract ideas, natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I).
Abstract ideas include mathematical concepts (including formulas, equations and calculations), and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)).
Laws of nature and natural phenomena include principles, relations, and products that are naturally occurring or do not have markedly different characteristics compared to what occurs in nature (MPEP 2106.04(b)).
The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than an abstract idea and a natural phenomenon.
Step 1: The Four Categories of Statutory Subject Matter (MPEP 2106.03)
The claims are directed to a method (claims 1-7 and 9-12) and a system (claim 23), which fall under categories of statutory subject matter.
Step 2A, Prong One: Whether the Claims Set Forth or Describe a Judicial Exception (MPEP 2106.04 § II.A.1)
‘Mathematical concepts’ are relationships between variables and numbers, numerical formulas or equations, or acts of calculation, which need not be expressed in mathematical symbols (MPEP 2106.04(a)(2) § I). The claims recite elements which encompass mathematical concepts, at least under their broadest reasonable interpretation, including:
“associating [input] data to each of the plurality of structure nodes” (claims 1 and 23) wherein “a p-value is determined for each correlation associated between the [input] data and the plurality of structure nodes, and is compared to a significance level, wherein only pair-wise correlations with p-values less than the significance level are used to generate the corresponding data structure” (claim 3), i.e., calculating statistics and organizing data based thereon.
The recited acts of calculation constitute mathematical concepts.
‘Mental processes’ are processes that can be performed in the human mind at least with use of a physical aid, e.g., a slide rule or pen and paper (MPEP 2106.04(a)(2) § III). The recited acts of calculation are practicably performable in the human mind, rendering them as mental processes. Additionally, the claims recite elements that encompass further processes that are practicably performable in the human mind, at least under their broadest reasonable interpretation, including:
“generat[ing]…data structure[s] from [input] data” (claims 1 and 23), i.e., organizing data;
“assigning a plurality of structure nodes” (claims 1 and 23), i.e., grouping information;
“comparing the first… and the second data structure[s]” (claims 1 and 23), wherein:
“comparing… includes comparing a number and/or density of inverse correlations in [each] data structure” (claim 4),
“comparing… includes comparing the number and/or density of correlations between different groups of structure nodes” (claim 6), and
“comparing… includes comparing the number and/or density of correlations between groups of structure nodes located respectively in the frontal lobe and the parietal and occipital lobes” (claim 7);
“determining patient response to the neuropharmacological intervention” (claims 1 and 23), wherein:
“efficacy is established by reduction in number and/or density of correlations between anterior and posterior brain regions of the first… and the second data structure[s]” (claim 11); and
“defining groups which contain [particular types of] structure nodes” (claim 5), i.e., grouping information based on representative nature.
The recited steps of evaluating information, which are practicably performable in the human mind, constitute mental processes.
Hence, the claims recite elements that, individually and in combination, constitute an abstract idea.
The claims further recite the following claim elements, which indicate reliance of the claimed invention on natural phenomena and/or laws of nature (MPEP 2106.04(b)):
obtained data is “indicative of a physical structure of a plurality of cortical regions” (claims 1 and 23), wherein “the physical structure is cortical thickness and/or surface area” (claim 2);
organized data “represent[s] a structural correlation network among the cortical regions of the brain” (claims 1 and 23);
analyzed groupings of data (e.g., “structure nodes”):
“correspond[] to cortical regions of the brain” (claims 1, 5 and 23),
“correspond[] to homologous or non-homologous lobes” (claim 5), and
“[are] located respectively in the frontal lobe and the parietal and occipital lobes” (claim 7); and
analysis of the obtained data achieves the function of “determining patient response to the neuropharmacological intervention” (claims 1 and 23), wherein “efficacy is established by reduction in number and/or density of correlations between anterior and posterior brain regions of the… data structure[s]” (claim 11).
The physical structure of a plurality of cortical regions of a given human brain (e.g., the brain of a patient diagnosed with a neurocognitive disease) is a naturally occurring phenomenon, as are the physical properties arising therefrom (e.g., cortical thickness and surface area). The relationship between observed changes in data indicative of said physical properties with respect to given cortical regions and patient response to a neuropharmacological intervention (e.g., indication of efficacy by an observed reduction in number and/or density of correlations between anterior and posterior brain regions) is a consequence of underlying biology.
Electrical activity within a given human brain is likewise naturally occurring. The relationship between observed electrical activity patterns within the brain of a patient and susceptibility of the patient to neurological disorders is likewise a consequence of underlying biology. These naturally-occurring relationships are laws of nature.
See relevant discussion in Mayo Collaborative Servs. v. Prometheus Labs., 566 U.S. 66 (2012) of ineligible claims as directed to a relationship between observed biomarker data and determined drug response that, although requiring administration of a drug (i.e., human action) to trigger a manifestation in a particular person, nonetheless was held to be a consequence of underlying biological processes (i.e., a natural law) that exists in principle apart from any human action (566 U.S. at 77).
Hence, the claims recite elements that, individually and in combination, constitute a natural phenomenon.
The claims must therefore be examined further to determine whether they integrate these judicial exceptions into a practical application (MPEP 2106.04(d)).
Step 2A, Prong Two: Whether the Claims Contain Additional Elements that Integrate the Judicial Exception(s) into a Practical Application (MPEP 2106.04 § II.A.2)
The claims recite additional elements that gather data necessary for performance of claimed method steps, including:
“obtain[ing] structural neurological data from the plurality of patients diagnosed with the neurocognitive disease before the neuropharmacological intervention… [and] further structural neurological data from the plurality of patients after neuropharmacological intervention” (claims 1 and 23), wherein:
the data is derived from images obtained by “imaging the plurality of patients using magnetic resonance imaging (MRI), positron emission tomography (PET), and/or computerized tomography (CT)” (claims 1, 12 and 23); and
“the neuropharmacological intervention is a disease modifying pharmaceutical” (claims 9 and 11), and
“the neuropharmacological intervention is a symptomatic treatment” (claim 10).
Obtaining data indicative of the physical structure of cortical regions, or of electrical activity within the brain of a patient, amounts to mere observation of natural phenomena. Gathering of data amounting to mere observation of natural phenomena, which is required for performance of method steps embodying abstract ideas, amounts to necessary data gathering activity. Necessary data gathering is considered to be insignificant pre-solution activity, and as such insufficient to integrate the judicial exceptions into a practical application (MPEP 2106.05(g)).
See discussion in Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015) of ineligible claims directed to “detecting the presence of a naturally occurring thing” (788 F.3d at 1378), and further discussion in Rapid Litig. Mgmt. v. CellzDirect, Inc., 827 F.3d 1042 (Fed. Cir. 2016) of eligible claims reciting significantly more than merely “observing or identifying the ineligible concept itself” (827 F.3d at 1048).
Performance of the recited clinical imaging techniques (e.g., magnetic resonance imaging) requires operation of particular machines (e.g., an MRI scanner). However, active performance of such operations is not required under the broadest reasonable interpretation of the claims. The claims require deriving (i.e., gathering) structural neurological data from images obtained with these techniques, which encompasses “receiving… data that has been previously recorded” (as discussed in the specification at pg. 7, para. 6).
Furthermore, the inclusion of machines which merely perform necessary data gathering does not amount to significantly more than the inclusion of necessary data gathering activity. Thus, affirmative requirement that a user perform the recited clinical imaging techniques would be insufficient to integrate the judicial exceptions into a practical application (MPEP 2106.05(b) § III).
The claims further recite additional elements that output results of claimed functions embodying abstract ideas, including:
“presenting the first… and the second data structure[s]” (claim 23).
Data output is considered to be insignificant post-solution activity, and as such
insufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g))
The claims further recite additional elements that constitute, and/or require use of, computer hardware configured to perform claimed functions, including:
“computer-implemented” (claim 1); and
“A system… comprising: at least one processor configured to” perform claimed functions, including “via a display” (claim 23).
The claims do not describe any specific computational steps by which claimed computer hardware performs or carries out functions drawn to the judicial exceptions, nor do they provide any details of how specific structures of computer hardware are used to implement these functions. The claims state nothing more than that conventional computer hardware (e.g., a processor) performs functions drawn to the judicial exceptions, and are therefore mere instructions to apply the judicial exceptions using computer hardware. As such, the claims do not integrate the judicial exceptions into a practical application (see MPEP 2106.04(d) § I and 2106.05(f)).
No further additional elements are recited.
When the claims are considered as a whole: they do not improve the functioning of a computer, other technology, or technical field (MPEP 2106.04(d)(1) and 2106.05(a)); they do not apply the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition (MPEP 2106.04(d)(2)); they do not implement the judicial exceptions with, or in conjunction with, a particular machine (MPEP 2106.05(b)); they do not effect a transformation or reduction of a particular article to a different state or thing (MPEP 2106.05(c)); and they do not apply or use the judicial exceptions in some other meaningful way beyond linking the use of the judicial exceptions to a particular technological environment and/or field of use (e.g., magnetic resonance imaging and neuropharmacological treatment; MPEP 2106.05(e) and 2106.05(h)).
Therefore, the claims do not integrate the judicial exceptions into a practical application. See MPEP 2106.04(d) § I.
Because the claims recite an abstract idea and a natural phenomenon, and do not integrate those judicial exceptions into a practical application, the claims are directed to those judicial exceptions. Claims that are directed to judicial exceptions must be examined further to determine whether the additional elements besides the judicial exceptions render the claims significantly more than the judicial exceptions. Additional elements besides the judicial exceptions may constitute inventive concepts that are sufficient to render the claims significantly more (MPEP 2106.05).
Step 2B: Whether the Claims Contain Additional Elements that Amount to an Inventive Concept (MPEP 2106.05)
As noted above, several recited additional elements amount to insignificant extra-solution activity. Mere addition of insignificant extra-solution activity does not amount to an inventive concept that would render the claims significantly more than the recited judicial exceptions, particularly when the activities are well-understood or conventional (MPEP 2106.05(g)). The conventionality of recited additional elements that amount to insignificant extra-solution activity must be further considered.
Recited additional elements amounting to insignificant extra-solution activity encompass the following processes, which are indicated as conventional activities and/or activities that may be performed with commercially-available products by the instant specification (see MPEP 2106.07(a) § III):
obtaining structural neurological data via MRI, CT and PET (pg. 3, para. 2; pg. 12, para. 1: “the structural neurological data may be obtained via magnetic resonance imaging, computed tomography, or positron emission tomography for each patient. These techniques are well known per se to those skilled in the art”; pg. 22, para. 1: “The multi-side source imaging data sets, used to generate the correlation matrices discussed below, were standard T1-weighted MRI images acquired using… train scanners… from three manufacturers (Philips, GE, and Siemens). MRI images in the ABC36 cohort were all acquired using the same (Philips) 3T scanner”).
Additionally, recited additional elements amounting to insignificant extra-solution activity encompass the following computer-implemented functions, which the courts have held as coextensive with a general-purpose computer and/or well-understood, routine and conventional:
obtaining data, i.e., receiving electronic data (In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1316 (Fed. Cir. 2011); EON Corp. IP Holdings LLC v. AT&T Mobility LLC, 785 F.3d 616, 622 (Fed. Cir. 2015)), including:
receiving data over a network (buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355 (Fed. Cir. 2014); OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015)), and
retrieving information from memory (OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015); Versata Dev. Group, Inc. v. SAP America, Inc., 793 F.3d 1306, 1334 (Fed. Cir. 2015)); and
presenting data structures via a display, i.e., displaying particular data (Electric Power Group, LLC v. Alstom S.A., 830 F.3d 1350, 13555 (Fed. Cir. 2016); Interval Licensing LLC v. AOL, Inc., 896 F.3d 1335, 1344-45 (Fed. Cir. 2018)).
Hence, the encompassed extra-solution activity is considered well-understood, routine and conventional. Well-understood, routine and conventional activity is insufficient to constitute an inventive concept that would render the claims significantly more than judicial exceptions (MPEP 2106.05(d)).
Mere instructions to implement judicial exceptions using a computer are, when considered individually, similarly insufficient to constitute an inventive concept that would render the claims significantly more than said judicial exceptions (see MPEP 2106.05(f)).
When the claims are considered as a whole, they do not integrate the judicial exceptions into a practical application; they do not confine the use of the judicial exceptions to a particular technology; they do not solve a problem rooted in or arising from the use of a
particular technology; they do not improve a technology by allowing the technology to
perform a function that it previously was not capable of performing; and they do not
provide any limitations beyond generally linking the use of the judicial exceptions to a particular technological environment and/or field of use (e.g., magnetic resonance imaging and neuropharmacological treatment; MPEP 2106.05(e) and 2106.05(h)).
Therefore, the claims do not provide an inventive concept and/or significantly more than the judicial exceptions themselves. See MPEP 2106.05.
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole, are directed to judicial exceptions and lack an inventive concept. Hence, the claimed invention does not constitute significantly more than the judicial exceptions, so the claims are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Response to Arguments - Claim Rejections Under 35 USC § 101
In the Remarks filed 10/14/2025, Applicant traverses the rejection under 35 USC § 101 and presents supporting arguments.
Applicant notes that the amended claims recite a computer-implemented method, and alleges that the method does not include any steps that can be practically performed in the human mind (pg. 11, para. 2).
Mental processes include both processes which can be performed mentally as claimed, and processes “which are the equivalent of human mental work” (CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1371 (Fed. Cir. 2011)) as claimed. The courts have consistently held that the mere computer implementation of processes which can be performed mentally does not alter their nature as equivalent to human mental work. For example, in SAP America, Inc. v. InvestPic, LLC, 898 F.3d 1161 (Fed. Cir. 2018; hereafter “SAP America”), the court held that computer-implemented method claims comprising a series of mathematical calculations were directed to abstract ideas without significantly more (898 F.3d at 1163).
As in SAP America (see 898 F.3d at 1168-70), there is nothing in the instant specification to indicate that claimed computer hardware is more than off-the-shelf computer technology having conventional functionality. The claims recite processes that may be performed mentally (e.g., with pen and paper) but for the recitation of additional limitations specifically requiring their performance using computer hardware. These claimed acts are therefore considered as the equivalent of human mental work, i.e., mental processes. Thus, the argument of claimed computer-implementation is unpersuasive.
Applicant alleges that the claims do not set forth or describe any mathematical relationships, calculations, formulas or equations using words or mathematical symbols, and so do not recite any mathematical concepts (pg. 11, para. 2).
The claims recite a process of “associating [input] data to each of the plurality of structure nodes” (claims 1 and 23) wherein “a p-value is determined for each correlation associated between the [input] data and the plurality of structure nodes, and is compared to a significance level, wherein only pair-wise correlations with p-values less than the significance level are used to generate the corresponding data structure” (claim 3). These limitations encompass acts of calculation, which are mathematical concepts. Thus, the argument against reciting mathematical concepts is unpersuasive.
Applicant alleges that each claim integrates any recited judicial exceptions into a practical application, e.g., claim 1 recites high accuracy assessment of a neuropharmacological intervention’s efficacy at treating a patient which is an improvement to technology for assessing a neuropharmacological intervention (pg. 11, para. 3). Applicant further alleges that the claimed method “provides a more accurate technique for assessing”, and “facilitates more accurate assessment of”, the efficacy of a neuropharmacological intervention and points to excerpts of the specification (found at pg. 6, lines 11-14 and 15-17) for support (pg. 11, para. 4 – pg. 13, para. 1).
The fact that a method is accurate, or useful for some purpose, does not implicitly render it as an improvement to technology. The cited excerpts do not indicate that technical elements of the claimed method provide a more accurate technique for assessing, or facilitate more accurate assessment of, the efficacy of a neuropharmacological intervention as compared to technology previously employed in the field of the invention.
In describing the claimed system, the instant specification simply states that “a computer system can be provided, the system including: one or more processors configured to” perform claimed functions (pg. 17, para. 1). In this way, the specification underscores the inclusion of general-purpose computer hardware within the scope of the claimed system. It is unclear how the claimed technical elements, encompassing general-purpose computer hardware (e.g., a processor), provide improved functioning of the claimed system over technology previously employed. The invention does not appear to provide technical improvement, thus the argument is found unpersuasive.
Applicant notes that amended claim 23 recites similar language to claim 1, and alleges that claim 23 is patent eligible for the same reasons discussed with respect to claim 1 (pg. 13, para. 3). As the arguments with respect to claim 1 are found unpersuasive, they likewise found unpersuasive with respect to claim 23.
For the above reasons, the arguments are found unpersuasive and the rejection is maintained with respect to the pending claims.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 USC §§ 102 and 103 is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 USC § 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.
Claims 1-2, 5-7, 9, 12 and 23 are rejected under 35 USC §§ 102(a)(1) and 102(a)(2) as being anticipated by Raj (US 2016/0300352; effectively filed 3/20/2013; corresponds to WO 2014/153466 listed on IDS filed 9/29/2021; previously cited). This rejection is maintained from the previous Office action, and has been revised to address the amended claims (filed 10/14/2025).
Claim 1 recites a computer-implemented method of determining patient response among a plurality of patients diagnosed with a neurocognitive disease to a neuropharmacological intervention, comprising steps of: obtaining structural neurological data from the patients, at least in part by deriving the data from images obtained by imaging the patients using magnetic resonance imaging (MRI), positron emission tomography (PET), and/or computerized tomography (CT) before the neuropharmacological intervention, indicative of a physical structure of a plurality of cortical regions; generating a first data structure by: assigning a plurality of structure nodes, corresponding to cortical regions of the brain, and associating structural neurological data from multiple patients to each of the structure nodes; obtaining further data from the patients, at least in part by deriving the data from images obtained by imaging the patients using magnetic resonance imaging (MRI), positron emission tomography (PET), and/or computerized tomography (CT) after the neuropharmacological intervention, indicative of the physical structure of the plurality of cortical regions; generating a second data structure by: associating further structural neurological data from multiple patients to each of the structure nodes; and comparing the first and second data structures, thereby determining patient response to the neuropharmacological intervention.
With respect to claim 1, Raj discloses analytical methods comprising steps of: obtaining images of the brain, i.e., structural neurological data, from patients (para. 0052); parcellating the obtained structural data and performing whole brain tractography, thereby producing a network model having nodes corresponding to cortical regions and edges proportional to the number and strength of connections between the nodes, and further generating a connectivity matrix (i.e., a form of data structure) for each patient by computing statistical correlation in neural activity between any two regions, i.e., pairwise correlation (paras. 0053-54, 0062 and 0065; Fig. 5); and comparing analytical output (e.g., a vector dot product) to reference standards to diagnose disease state (para. 0075).
Raj states that preferred subjects include human subjects suffering from a given disease or condition, and are generally diagnosed with the condition (para. 0133). Raj exemplifies application to numerous neurocognitive diseases including Alzheimer’s disease, behavioral frontotemporal dementia, and Parkinson’s disease (para. 0075 and 0118). In this way, Raj discloses application to patients that have been diagnosed with a neurocognitive disease.
Raj further discloses application of their methods to testing of a medical intervention, wherein: a medical image of a patient’s brain is obtained and analyzed according to the disclosed methods; an intervention is administered; a second medical image of the patient’s brain is obtained, after a given time period, and analyzed according to the disclosed methods; and analytical results are compared to determine the efficacy of the intervention (para. 0067). In other words, obtaining structural neurological data before and after an intervention and comparing to thereby determine patient response to the intervention. Raj exemplifies assessment of efficacy in clinical trials of drug interventions for central nervous system diseases (para. 0140), i.e., neuropharmacological interventions.
Raj does not disclose direct comparison of generated data structures (e.g., comparison of values within each connectivity matrix). However, as explained above, Raj does explicitly disclose comparison of output derived from connectivity matrices, i.e., indirect comparison of generated data structures. The scope of the claimed step of comparing the first data structure and the second data structure is considered to encompass indirect comparison of correlation matrices. Thus, Raj is considered to disclose a species of the claimed genus of comparing the first data structure and the second data structure. See MPEP 2131.02.
With respect to claim 2, Raj discusses comparison, between subjects, of MRI-derived volumetrics and cortical thickness (para. 0129). Raj thus discloses that MRI data is indicative of cortical thickness.
With respect to claim 5, Raj discloses computing correlations in neural activity between any two brain regions (para. 00054), and further discloses decomposition of the connectivity matrix into ‘eigen-modes’, correlated networks of cortical regions connected by tracts of white matter (paras. 0054, 0057 and 0088).
Raj exemplifies various eigen-modes exhibiting characteristic atrophy across a number of regions, such as a “2nd eigen-mode” (para. 0090; Figs. 6 and 8) that shows atrophy correlated between ‘medial’ and ‘lateral’ temporal regions (i.e., between regions corresponding to homologous lobes), and a “3rd eigen-mode” (para. 0091; Figs. 7 and 9) that shows atrophy correlated between the ‘lateral temporal’ and several ‘frontal’ regions (i.e., between regions corresponding to non-homologous lobes).
With respect to claim 6, Raj discloses calculating a vector dot product of each generated eigen-mode with the subject’s atrophy pattern, wherein the product measures of the contribution of each eigen-mode to said pattern, and comparing the output product to reference projections of eigen-modes onto known disease patterns (para. 0075). In this way, Raj discloses comparing associations between different groups of structural nodes.
With respect to claim 7, Raj exemplifies analysis of regions located in the frontal, parietal and occipital lobes (para. 0130; Fig. 25).
With respect to claim 9, Raj discloses application to assessing efficacy of a medical intervention in a clinical trial (para. 0067), and exemplifies clinical trials of drug interventions for central nervous system diseases (para. 0140), i.e., disease-modifying pharmaceuticals. This application necessarily includes administration of a disease-modifying pharmaceutical.
With respect to claim 12, Raj discloses that images may be generated via MRI (para. 0054).
Claim 23, is directed to a computer system comprising: a processor configured to perform recited functions of substantive similarity to the processes recited in claim 1, and further configured to perform at least one of: presenting the first data structure and second data structure via a display, or comparing the first data structure and the second data structure, thereby determining the patient responder to the neuropharmacological intervention.
Raj discloses implementation of their methods with computer hardware and software (para. 0145), including a processor (para. 0145) and display screens for visual presentation of output (para. 0147), and a computer-readable storage medium storing instructions that, when executed, program a processor to perform the methods (para. 152). The disclosure of Raj is considered to apply to the functional limitations of claim 23 in the same manner as detailed with respect to the process limitations of claim 1.
In this way the disclosure of Raj anticipates the limitations of claims 1-2, 5-7, 9, 12 and 23. Thus, the invention is anticipated.
Response to Arguments - Claim Rejections Under 35 USC § 102
In the Remarks filed 10/14/2025, Applicant traverses the rejection under 35 USC § 102 and alleges deficiencies of Raj with respect to the amended claims.
In particular, Applicant notes that amended claim 1 describes obtaining and using data from a plurality of patients while the technique described in Raj utilizes data from a single patient (pg. 9, para. 3 – pg. 10, para. 1). In fact, Raj discloses application of the described techniques to a cohort of subjects and comparison of effect sizes scaled across subjects (para. 0129). Raj is therein considered to at least inherently disclose obtaining and using data from a plurality of patients, and the argument is found unpersuasive..
Applicant notes that amended claim 23 similarly describes obtaining and using data from a plurality of patients, and alleges that claim 23 patentably distinguishes over Raj for the same reason as discussed with respect to claim 1 (pg. 10, paras. 3-4). As the argument with respect to claim 1 is found unpersuasive, it is likewise found unpersuasive with respect to claim 23.
Therefore, the rejection is maintained with respect to the pending claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 USC § 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 USC § 102(b)(2)(C) for any potential 35 USC § 102(a)(2) prior art against the later invention.
Claim 3 is rejected under 35 USC § 103 as being unpatentable over Raj, as applied to claim 1 above, in view of Zeman et al (US 2013/0060125; effectively filed 4/16/2010; corresponds to WO 2011/127609 listed on IDS filed 9/29/2021; previously cited). This rejection is maintained from the previous Office action, and has been revised to address the amended claim (filed 10/14/2025).
With respect to claim 3, Raj discloses gathering of data from a number of different imaging modalities, including MRI, PET and electroencephalography (EEG, para. 0054). Raj also discusses calculation of p-values to determine statistically significant pair-wise correlations between parcellated diseased and healthy volumes, i.e., thickness data grouped by cortical region (para. 0159-60). Raj exemplifies determination of statistical significance “at the level of e<COS”, i.e., as compared to a given significance level (para. 0159). However, Raj does not disclose that only pair-wise correlation with determined p-values less than the significance level are used to generate the corresponding data structure.
Zeman discusses methods and an apparatus for processing of encephalography data to yield components corresponding to modular areas of the brain (Abstract), and discloses user-defined thresholding of calculated pairwise volumetric spectrum coefficients (i.e., graphical edge boundaries) to define an equivalent structural source volume (paras. 0137-39). Zeman exemplifies thresholding according to significance levels, and presentation of calculated coefficients including only threshold-satisfying ‘primary relationships’, i.e., pairwise correlations of greater significance than p < 0.02 (para. 0207; Fig. 47).
An invention would have been obvious to one of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, said practitioner would have implemented thresholding of pairwise correlations based on determined p-values less than a significance level, as taught by Zeman, in combination with the analytical methodology of Raj, because Raj discloses analysis of encephalography data but does not further describe particular means for accomplishing such analysis, while Zeman teaches that pairwise correlations with determined p-values greater than a significance level represent primary relationships within the brain of a patient (para. 0207).
Zeman thus presents evidence that implementing such p-value thresholding would allow for presentation of most-relevant correlations. Said practitioner would have had a reasonable expectation of success because Raj and Zeman both discuss analysis of network connectivity within the brains of patients with neurological diseases based on imaging data.
In this way the disclosure of Raj, in view of Zeman, makes obvious the limitations of claim 3. Thus, the invention is prima facie obvious.
Claim 4 is rejected under 35 USC § 103 as being unpatentable over Raj, as applied to claim 1 above, in view of Etkin et al (WO 2017/172487; effectively filed 3/28/2016; on IDS filed 9/29/2021; previously cited). This rejection is maintained from the previous Office action, and has been revised to address the amended claim (filed 10/14/2025).
With respect to claim 4, Raj discloses performance of whole brain tractography, using obtained structural neurological data, to produce a network model having edges proportional to the number and strength of connections between cortical regions, and therefrom generating a connectivity matrix by computing statistical correlation in neural activity between any two regions, i.e., a data structure of correlations (paras. 0053-54, 0062 and 0065; Fig. 5).
Raj exemplifies analysis of regions located in the frontal, parietal and occipital lobes (para. 0130; Fig. 25), and further discloses comparing analytical output derived from correlation matrices (para. 0075). However, Raj does not disclose comparing number and/or density of inverse correlations in the data structures.
Etkin discusses methods for analysis of abnormal network connectivity within the brains of patients with posttraumatic stress disorder (paras. 0010-11), including structural and functional connectivity of network nodes (i.e., cortical regions) based on data measured via functional magnetic resonance imaging (fMRI) or electroencephalography (para. 0048). Etkin teaches quantification of pairwise regional connectivity in terms of internodal distances, wherein distances between two nodes are the inverse of correlations in their measured activity (paras. 0016, 0061-63 and 0093).
Etkin further teaches that patients having PTSD with impaired delayed recall are significantly characterized against patients without impaired delayed recall by patterns in network connectivity metrics determined via the disclosed methods, such as lower average network efficiency (paras. 0166-67; Fig. 2B).
An invention would have been obvious to one of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, said practitioner would have implemented analysis of inverse correlations, as taught by Etkin, in combination with the analytical methodology of Raj, because Etkin teaches that patterns of inverse network correlation metrics are significantly different between patients with particular neurological disease characteristics (paras. 0166-67).
Etkin thus presents evidence that implementing analysis of such inverse correlations would allow for application of the methodology of Raj to differential determination of impaired delayed recall in patients with PTSD. Said practitioner would have had a reasonable expectation of success because Raj and Etkin both discuss analysis of network connectivity within the brains of patients with neurological diseases based on imaging data.
In this way the disclosure of Raj, in view of Etkin, makes obvious the limitations of claim 4. Thus, the invention is prima facie obvious.
Claim 10 is rejected under 35 USC § 103 as being unpatentable over Raj, as applied to claim 1 above, in view of Wischik et al (US 2010/0280975; effectively filed 11/5/2007; on IDS filed 12/8/2023; previously cited). This rejection is maintained from the previous Office action.
With respect to claim 10, Raj discloses application to assessing efficacy of a medical intervention in a clinical trial (para. 0067), and exemplifies clinical trials of drug interventions for central nervous system diseases (para. 0140). Raj does not disclose embodiments wherein the intervention is a symptomatic treatment.
Wischik discusses methods and systems for assessing the efficacy of a pharmaceutical for treatment or prophylaxis of a cognitive disorder (Abstract), and teaches analysis of changes in functional bran scan images acquired via single photon emission computed tomography (paras. 0169 and 0244). Wischik exemplifies assessment of patients treated with acetylcholine esterase (AChE) inhibitors, i.e., symptomatic treatments (para. 0221, Table 5 caption; see para. 0006) and teaches that that there have been numerous examples of clinical trials featuring such symptomatic treatments (para. 0006).
An invention would have been obvious to one of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, said practitioner would have applied the analytical methodology of Raj to assessment of symptomatic treatments, as exemplified by Wischik, because Wischik teaches that there have been numerous clinical trials of such treatments (para. 0006). In other words, assessing efficacy of symptomatic treatments has historically been a frequent goal in the field of the invention.
Wischik thus provides evidence that application of the methodology of Raj to assessing efficacy of symptomatic treatments presents an application of great practical relevance to the field of the invention. Said practitioner would have had a reasonable expectation of success because Raj and Wischik both discuss analysis of network connectivity within the brains of patients with neurological diseases based on data measured via structural imaging techniques.
In this way the disclosure of Raj, in view of Wischik, makes obvious the limitations of claim 10. Thus, the invention is prima facie obvious.
Claim 11 is rejected under 35 USC § 103 as being unpatentable over Raj, as applied to claim 1 above, in view of Zeman and Horwitz et al (NeuroReport 6(17): 2287-2292; published 11/27/1995; previously cited). This rejection is maintained from the previous Office action, and has been revised to address the amended claim (filed 10/14/2025).
With respect to claim 11, Raj discloses application of their analytical methodology to assessing efficacy of a medical intervention in a clinical trial (para. 0067), and exemplifies clinical trials of drug interventions for central nervous system diseases (para. 0140). Raj does not disclose establishment of efficacy based on reduction in number and/or density of correlations between anterior and posterior brain regions.
Zeman exemplifies application of their analytical methodology to assessing drug treatment efficacy in cases where compensation for a disease or dysfunction is believed to be taking place, the goal is to show that the activities of compensatory systems decrease when the drug treatment is consumed (para. 0263). Zeman does not teach establishment of efficacy based on reduction in number and/or density of correlations between anterior and posterior brain regions.
Horwitz discusses neuropathological changes seen in Alzheimer’s disease (pg. 2287, l. column) and teaches that Alzheimer’s patients (referred to in the text as “DAT patients”, patients with ‘dementia of the Alzheimer’s type’) exhibit increased utilization of a prefrontal compensatory network linking anterior and posterior cortical areas (pg. 2292, l. column), i.e., increased number and/or density of correlations between anterior and posterior brain regions.
An invention would have been obvious to one of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, said practitioner would have implemented establishment of efficacy based on reduction in number and/or density of correlations between brain regions within a compensatory network, in combination with the analytical methodology of Raj, because Raj discloses application of their analytical methodology to assessing efficacy of drug treatments (paras. 0067 and 0140) while Zeman teaches application of such analytical methodology to assess drug treatment efficacy based on reduction in activity of compensatory networks.
Zeman thus presents evidence that establishing efficacy in this manner would allow for application of the methodology of Raj to assessment of drug treatment efficacy in cases where the treated disease is characterized by increased compensatory activity. Said practitioner would have had a reasonable expectation of success because Raj and Zeman both discuss analysis of network connectivity within the brains of patients with neurological diseases based on imaging data.
Furthermore, said practitioner would have implemented establishment of efficacy based on reduction in number and/or density of correlations between anterior and posterior brain regions in particular, in combination with the analytical methodology of Raj, in view of Zeman, because Horwitz teaches that Alzheimer’s disease is characterized by increased activity of a compensatory network linking anterior and posterior brain regions (pg. 2292, l. column). Horwitz thus presents evidence that establishing efficacy in this manner would allow for application of the methodology of Raj, in view of Zeman, to assessment of drug treatment efficacy against Alzheimer’s disease.
Said practitioner would have had a reasonable expectation of success because Raj, Zeman and Horwitz all discuss analysis of network connectivity within the brains of patients with neurological diseases based on data measured via brain imaging techniques. In this way the disclosure of Raj, in view of Zeman and Horwitz, makes obvious the limitations of claim 11. Thus, the invention is prima facie obvious.
Conclusion
At this point in prosecution, no claim is allowed.
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/T.C.S./Examiner, Art Unit 1685
/JESSE P FRUMKIN/ Primary Examiner, Art Unit 1685 January 24, 2026