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 .
Response to Amendment
This action is in response to the remarks filed on 04/25/2025.
The amendments filed on 04/25/2025 have been entered. Applicant has presently canceled claim 79. Accordingly claims 49, 52-54, 74-75, 78, and 80-81 are pending. Claims 49, 52, and 74 are presently amended.
The previous objections to the claims have been withdrawn in light of applicant's amendments to claims 52, 74 and the canceling of claim 79.
The previous rejections of the under 35 U.S.C 112(b) have been withdrawn in light of applicant's amendments to claims 49, 52, and 74.
Response to Arguments
Applicant's arguments filed 04/25/2025 regarding the 35 U.S.C. 101 rejection of the claims have been fully considered but they are not persuasive.
In particular applicant argues that the claims do not recite a judicial exception, specifically they do not recite a mental process because the steps are not practically performed in the human mind. In response examiner notes that the obtaining steps that involve multivoxel pattern analysis now amended to recite using a support vector machine are still encompass mental observations or evaluations, e.g., a computer programmer’s mental identification of the binding potential pattern in the PET scans.
Applicant's arguments filed regarding the prior art rejections of the claims have been fully considered but they are not persuasive.
First, applicant argues that Mahmoudi fails to disclose multivoxel pattern analysis (MVPA) of PET or SPECT. However, primary reference Parsey discloses analysis of PET images (and MRI). Mahmoudi was relied on to teach the claimed analysis not the type of image. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant further argues that Zuckerman-Stark fails to teach MVPA of PET or SPECT or the voxel-level BPF values of the brain . However, Zuckerman-Stark was merely relied on to teach the number of features being 25 to 500. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Finally, applicant also argues that Parsey fails to disclose comparing across multiple regions in the brain of the subject as claimed. Examiner respectfully disagrees because Parsey discloses multiple regions in the brain of the subject including midbrain (“a small region in the midbrain” [0217]), parahippocampal gyrus, and ventral prefrontal cortex (“In some embodiments, the region of interest is selected from the group consisting of the raphe nucleus, dorsolateral prefrontal cortex, medial prefrontal cortex, orbito-frontal cortex, anterior cingulate cortex, subgenual prefrontal cortex, temporal cortex, parietal cortex, occipital cortex, amygdala, uncus, hippocampal formation, entorhinal cortex, parahippocampal gyrus, insula, dorsal raphe nuclei, and cerebellum.” [0060]) as claimed.
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.
Claims 49, 52-54, 78, and 80-81 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Analysis step 1 of Subject Matter Eligibility Test
The claims are directed to a process (i.e., a method of identifying a subject at high risk for or having a major depressive disorder) of claims 49, 52-54, 74-75, 78, and 80-81.
Analysis step 2A, Prong I
The claims recite abstract ideas, in particular mental processes, e.g., concepts performed in the human mind (including an observation, evaluation, judgment, opinion).
Claim 49 recites “c. obtaining a serotonin 1A receptor binding potential BPF) pattern in the brain of the subject, wherein the serotonin 1A receptor binding potential pattern is obtained using multivoxel pattern analysis of PET or SPECT, wherein the multivoxel pattern analysis analyzes voxel-level BPF values across multiple regions in the brain of the subject, and wherein top 25 to 500 features based on support vector machine (SVM) with a filter feature selection are used in the multivoxel pattern analysis, wherein features are voxel-level BPF values, wherein the multiple regions in the brain of the subject comprise one or more regions selected from midbrain, parahippocampal gyrus, and ventral prefrontal cortex; d. comparing the serotonin 1A receptor binding potential pattern in the brain of the subject to a reference serotonin 1A receptor binding potential pattern; and e. determining that the subject is at high risk for or has a major depressive disorder when the serotonin 1A receptor binding potential pattern in the brain of the subject is substantially the same as a subject with major depressive disorder” which encompasses mental observations or evaluations.
Claims 52-54 further define the scans. Claim 78 further defines the multivoxel pattern analysis.
Analysis step 2A, Prong II
The judicial exception is not integrated into a practical application because the additional elements of the claim merely add insignificant extra-solution activity and are mere instructions to implement an abstract idea on a computer. See MPEP 2106.05 (f) and (g).
Claim 49 recites the limitation “a. introducing a radioligand capable of binding a serotonin 1A receptor into the subject; b. performing one or more scans of the subject, wherein the one or more scans comprise positron emission tomography (PET), single-photon emission computed tomography (SPECT), or a combination thereof” which is insignificant extra-solution activity, in particular mere data gathering. Claims 80 and 81 recite the limitation “train a classification model”. This limitation represents no more than mere instructions to apply the judicial exception on a computer. It can also be viewed as nothing more than an attempt to generally link the use of the judicial exception to the technological environment of computers.
Analysis step 2B
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the training of a classification model is an additional element that merely results in instructions to implement an abstract idea on a computer that is well-understood, routine, and conventional activity previously known to the industry. The remaining additional elements merely add insignificant extra-solution activity, in particular mere data gathering, to the judicial exception that are well-understood, routine, and conventional activities previously known to the industry.
Claims 49, 52-54, 78, and 80-81 are therefore directed to a judicial exception without significantly more. The claims are not patent eligible.
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.
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.
Claims 49, 52-54, 74-75, 78, and 80-81 are rejected under 35 U.S.C. 103 as being unpatentable over Parsey et al. (WO 2015/134762, September 11, 2015, citations used in this Office Action corresponding to the corresponding US pre-grant publication US 2017/0071522, hereinafter “Parsey”) in view of Mahmoudi, et al. (2012). Multivoxel pattern analysis for fMRI Data: A Review. Computational and Mathematical Methods in Medicine, 2012, 1–14 (hereinafter “Mahmoudi”) and Zuckerman-Stark et al. (US 2013/0310660, November 21, 2013, hereinafter “Zuckerman-Stark”).
Regarding claim 49, Parsey discloses a method of identifying a subject at high risk for (“The present invention provides a method of determining whether a subject is at risk for developing a depressive disorder comprising” [0124]) or having major depressive disorder (“determining whether the subject is afflicted with the depressive disorder” [0019]), comprising:
a. introducing a radioligand capable of binding a serotonin lA receptor into the subject (“introducing into the subject a positron emission tomography (PET) radioligand capable of binding with a serotonin 5-HT.sub.1A receptor” [0020]; also see [0125]);
b. performing one or more scans of the subject, wherein the one or more scans comprise positron emission tomography (PET), single-photon emission computed tomography (SPECT), or a combination thereof (“performing one or more PET scans of the subject” [0021]; also see [0126]);
c. obtaining a serotonin lA receptor binding potential (BPF) pattern in the brain of the subject, wherein the serotonin 1A receptor binding potential pattern is obtained using analysis of PET or SPECT (“determining, by analysis of the one or more PET images, a receptor binding potential of the PET radioligand for the serotonin 5-HT.sub.1A receptor in a region of interest in the subject” [0022]; also see “In some embodiments, the region of interest is in the brain.” [0059]; also see [0127]) wherein the analysis is across multiple region in the brain of the subject, wherein the multiple regions in the brain of the subject comprise one or more regions selected from midbrain (“a small region in the midbrain” [0217]), parahippocampal gyrus, and ventral prefrontal cortex (“In some embodiments, the region of interest is selected from the group consisting of the raphe nucleus, dorsolateral prefrontal cortex, medial prefrontal cortex, orbito-frontal cortex, anterior cingulate cortex, subgenual prefrontal cortex, temporal cortex, parietal cortex, occipital cortex, amygdala, uncus, hippocampal formation, entorhinal cortex, parahippocampal gyrus, insula, dorsal raphe nuclei, and cerebellum.” [0060]);
d. comparing the serotonin lA receptor binding potential pattern in the brain of the subject to a reference serotonin lA receptor binding potential pattern (“comparing the receptor binding potential value of the radioligand in the region of interest in the subject to a predetermined receptor binding potential threshold value” [0023]; also see [0128]); and
e. determining that the subject is at high risk for or has major depressive disorder when the serotonin lA receptor binding potential pattern in the brain of the subject is substantially the same as a subject with major depressive disorder (“Based on the data presented in FIG. 2, the threshold used for distinguishing male depressed from controls (raphe BP.sub.F=39 mL/cm.sup.3) also distinguishes male high risk offspring (HRO) from controls. HRO offspring are individuals who have at least one parent diagnosed with depression. Therefore this technology may be used to identify those at risk, while they are currently asymptomatic.” [0197]; also see [0024] and also see “In some embodiments, the depressive disorder is major depression.” [0065]).
Although Parsey further discloses various computer analyses on the PET data (“PET data analyses were performed as described previously (Parsey et al., 2005). Image analysis was performed using MATLAB (The Mathworks, Natick, Mass.) with extensions to the following open source packages: Functional Magnetic Resonance Imaging of the Brain's Linear Image Registration Tool (FLIRT) v5. (Oxford Center for Functional Magnetic Resonance Imaging of the Brain, Oxford, England) (Jenkinson & Smith, 2001), Brain Extraction Tool (BET) v1.2 (Oxford Centre for Functional Magnetic Resonance Imaging of the Brain) (Smith, 2002), and University College of London's Statistical Parametric Mapping (SPM5) (Wellcome Department of Imaging Neuroscience, London, United Kingdom) normalization (Ashburner & Friston, 1999) and segmentation routines (Ashburner & Friston, 2005). To correct for subjection motion during the PET scan, de-noising filter techniques were applied to later PET images. The eighth frame was used as a reference onto which all other frames were aligned using rigid body FLIRT. For co-registration, a mean of the motion-corrected frames was registered using FLIRT to the MRI. Time activity curves were generated by plotting the average regional activity within each co-registered PET frame over the time of the scan.” [0182]), Parsey fails to explicitly disclose wherein the serotonin 1A receptor binding potential (BPF) pattern is obtained using multivoxel pattern analysis of PET or SPECT, wherein the multivoxel pattern analysis analyzes voxel-level BPF values across multiple region in the brain of the subject, and wherein top 25 to 500 features based on support vector machine (SVM) with a filter feature selection are used in the multivoxel pattern analysis, wherein features are voxel-level BPF values.
However, Mahmoudi teaches, in the same field of endeavor, using multivoxel pattern analysis, wherein the multivoxel pattern analysis analyzes voxel-level values across multiple region in the brain of the subject (“Multivoxel pattern analysis (MVPA)
represents a promising technique that is currently exploited to investigate the information contained in distributed patterns of neural activity to infer the functional role of brain areas and networks.” Abstract; also see “Instead of assigning a P value to each voxel, clusters of voxels are created on the basis of an initial threshold, and then each cluster is assigned a P value [5, 12]. The resulting thresholded statistical maps display the brain regions whose BOLD activity significantly correlates with the cognitive functions under investigation
(Figure 1).” page 2), and wherein top features based on support vector machine (SVM) with a filter feature selection are used in the multivoxel pattern analysis (“Feature Selection and Dimensionality Reduction [...] Therefore, the dimensionality of the data needs to be significantly reduced, and informative features (voxels) have to be wisely selected in order to make the classification task feasible [...] SVM classifiers can also be used to perform feature selection [...]” pages 6-8).
Therefore before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to modify the invention of Parsey with wherein the serotonin 1A receptor binding potential (BPF) pattern is obtained using multivoxel pattern analysis of PET or SPECT, wherein the multivoxel pattern analysis analyzes voxel-level BPF values across multiple region in the brain of the subject, and wherein top features based on support vector machine (SVM) with a filter feature selection are used in the multivoxel pattern analysis as taught by Mahmoudi in order to analyze patterns of activity with neighboring voxels (Abstract of Mahmoudi) and to reduce dimensionality of data by finding informative features and ignoring uninformative sources of noise (page 7 of Mahmoudi).
Parsey modified by Mahmoudi is silent on the feature selection specifically being top 25 to 500 features.
However, Zuckerman-Stark teaches, in the same field of endeavor, wherein top 25 to 500 features based on a filter feature selection are used in the multivoxel pattern analysis (“Next Feature Selection step was performed. During the training phase features with maximum Fisher score were selected [...] During feature selection only the 100 highly ranked features were kept, the remaining features were removed from consideration.” [0195]-[0196]).
Therefore before the effective filing date of the claimed invention, it would have been obvious to one having ordinary skill in the art to provide the feature selection with top -25 to 500 features, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
Regarding claim 52, Parsey modified by Mahmoudi and Zuckerman-Stark discloses the limitations of claim 49 as stated above. Parsey further discloses wherein the one or more scans further comprise magnetic resonance imaging (MRI) (“the step (ii) further comprises carrying out one or more MRI scans of the subject.” [0048]).
Regarding claim 53, Parsey modified by Mahmoudi and Zuckerman-Stark discloses the limitations of claim 49 as stated above and Parsey further discloses wherein the entire brain is scanned (“In some embodiments, the region of interest is in the brain.” [0059]). Examiner notes that Mahmoudi also teaches wherein the entire brain is scanned (“The study showed that for both SVM and CVA, classification of individual time samples of whole brain data can be performed with no averaging across scans.” page 5; also see Fig. 1).
Regarding claim 54, Parsey modified by Mahmoudi and Zuckerman-Stark discloses the limitations of claim 49 as stated above and Parsey further discloses wherein an area of the brain is scanned chosen from the group consisting of the: anterior cingulate; amygdala; cingulate body; dorsolateral prefrontal cortex; hippocampus; insula; medial prefrontal cortex; occipital lobe; orbital prefrontal cortex; parietal lobe; parahippocampal gyrus; temporal lobe; raphe nuclei; and combinations thereof (“In some embodiments, the region of interest is selected from the group consisting of the raphe nucleus, dorsolateral prefrontal cortex, medial prefrontal cortex, orbito-frontal cortex, anterior cingulate cortex, subgenual prefrontal cortex, temporal cortex, parietal cortex, occipital cortex, amygdala, uncus, hippocampal formation, entorhinal cortex, parahippocampal gyrus, insula, dorsal raphe nuclei, and cerebellum.” [0060]).
Regarding claim 74, Parsey modified by Mahmoudi and Zuckerman-Stark discloses the limitations of claim 49 as stated above and Parsey further discloses further comprising administering to the subject a therapeutically effective amount of a therapeutic agent (“In some embodiments, the subject is treated with an anti-depressant. In some embodiments, the male subject is treated with an anti-depressant.” [0071]) or treating the subject with psychotherapy (“In some embodiments, the subject is treated with psychotherapy. In some embodiments, the male subject is treated with psychotherapy.” [0073]).
Regarding claim 75, Parsey modified by Mahmoudi and Zuckerman-Stark discloses the limitations of claim 74 as stated above and Parsey further discloses wherein the therapeutic agent is chosen from the group consisting of selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, tricyclic antidepressants, tetracyclic antidepressants, lithium, electroconvulsive therapy, rapid transcranial magnetic stimulation and related stimulation therapies, anticonvulsants, ketamine and monoamine oxidase inhibitors (MAOIs) (“In some embodiments of the above method, the male subject is treated with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, tricyclic antidepressants, tetracyclic antidepressants, or monoamine oxidase inhibitors (MAOIs).” [0121]; also see [0122]).
Regarding claim 78, Parsey modified by Mahmoudi and Zuckerman-Stark discloses the limitations of claim 49 as stated above and Parsey further discloses wherein the multiple regions in the brain of the subject comprise the whole brain of the subject (“In some embodiments, the region of interest is in the brain.” [0059]). Examiner notes that Mahmoudi also teaches wherein the multiple regions in the brain of the subject comprise the whole brain of the subject (“The study showed that for both SVM and CVA, classification of individual time samples of whole brain data can be performed with no averaging across scans.” page 5; also see Fig. 1).
Regarding claim 80, Parsey modified by Mahmoudi and Zuckerman-Stark discloses the limitations of claim 49 as stated above but fails to disclose wherein top 75 features are used to train a classification model.
However, Mahmoudi further teaches, in the same field of endeavor, wherein top features are used to train a classification model (“Martino et al. [31] developed the recursive feature elimination (RFE) algorithm which iteratively eliminates the least discriminative features based on multivariate information as detected by the classifier. For each voxel selection level, the RFE consists of two steps. First, an SVM classifier is trained on a subset of training data using the current set of voxels.” page 7).
Therefore before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to further modify the invention of Parsey with wherein top features are used to train a classification model as taught by Mahmoudi in order to reduce dimensionality of data by finding informative features and ignoring uninformative sources of noise (page 7 of Mahmoudi).
Parsey modified by Mahmoudi and Zuckerman-Stark fails to explicitly disclose top 75 features. However, before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to provide top 75 features, since it has been held that discovering an optimum value of a result effective variable, i.e., number of top features used to optimize performance of analysis, involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
Regarding claim 81, Parsey modified by Mahmoudi and Zuckerman-Stark discloses the limitations of claim 49 as stated above but fails to disclose wherein top 25 features are used to train a classification model.
However, Mahmoudi further teaches, in the same field of endeavor, wherein top features are used to train a classification model (“Martino et al. [31] developed the recursive feature elimination (RFE) algorithm which iteratively eliminates the least discriminative features based on multivariate information as detected by the classifier. For each voxel selection level, the RFE consists of two steps. First, an SVM classifier is trained on a subset of training data using the current set of voxels.” page 7).
Therefore before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to further modify the invention of Parsey with wherein top features are used to train a classification model as taught by Mahmoudi in order to reduce dimensionality of data by finding informative features and ignoring uninformative sources of noise (page 7 of Mahmoudi).
Parsey modified by Mahmoudi and Zuckerman-Stark fails to explicitly disclose top 25 features. However, before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to provide top 25 features, since it has been held that discovering an optimum value of a result effective variable, i.e., number of top features used to optimize performance of analysis, involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/A.A./ Examiner, Art Unit 3797
/CHRISTOPHER KOHARSKI/ Supervisory Patent Examiner, Art Unit 3797