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 .
Election/Restrictions
Applicant’s election without traverse of Invention I in the reply filed on 15 June 2026 is acknowledged.
Specification
The extremely lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 6 is objected to because of the following informalities:
Claim 6 refers to “the CA1” without specifically identifying this object, location, or element; all other abbreviated terms are properly defined such that this omission is more evident.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10 and 14 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 calls for referring the subject for a procedure “during which the presence of epileptiform spikes in the brain of said subject is detected” – as presented, the method requires that these spikes be detected in every subject. It appears the intent is to perform the procedure and then continue the method if spikes are detected, not to require them to be present in every subject.
Further, as presented, any detected epileptiform spikes result in a diagnosis of AD or MCI, regardless of any other potential source of spikes and without any sort of threshold or baseline that might provide nuance to identification. It is unclear if a single epileptiform spike that a subject experiences only one time ever would be sufficient to identify development of AD or MCI. Clarification is required.
Claim 1 continues by “providing the subject with a treatment capable of attenuating or reducing cortico-hippocampal hyperactivity, thereby delaying the onset of symptoms”. If the treatment is merely capable of attenuating activity, it is unclear how this inherently results in a delay of the onset of any symptoms in all occurrences. The same is found in claim 14. Clarification is required.
Claim 2 recites that “said subject is about to undergo general anesthesia”; it is unclear how the timing of this relates to the remainder of the method – whether the subject is “about to undergo” anesthesia prior to the referral for diagnostic anesthesia, or if the subject is “about to undergo” this anesthesia following the treatment, or if the diagnostic anesthesia itself is included in general anesthesia. Clarification is required.
Claim 5 recites “said epileptiform spikes are detected at the hippocampus”; claim 1 recites only that “the presence of epileptiform spikes in the brain of said subject is detected”, such that there is insufficient antecedent basis for the detection of spikes themselves when claim 1 only refers to the detection of the presence of spikes. Clarification is required.
Claim 7 recites “wherein detecting the presence of said epileptiform spikes in the brain of said subject during diagnostic anesthesia is performed by….”. Claim 1 does not recite actively detecting anything as part of the claimed method, let alone the presence of epileptiform spikes. At best, some detection of a presence of spikes takes place somehow during the anesthesia, but there is no recitation of active detection actually taking place nor is there recitation of detecting spikes themselves. Clarification is required.
Claim 10 recites “said DBS is applied to the thalamic nucleus reuniens”; it is unclear if this merely describes an inherent feature of DBS or if the intent is to define a method step further refining the “providing” of the treatment. Clarification is required.
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.
Claim(s) 1-10 is/are rejected under 35 U.S.C. 101 because the claimed invention, considering all claim elements both individually and in combination as a whole, do not amount to significantly more than a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea).
Claim 1 is a claim to a process, machine, manufacture, or composition of matter and therefore meets one of the categorical limitations of 35 U.S.C. 101. However, claim 1 meets the first prong of the step 2A analysis because it is directed to a/an abstract idea, as evidenced by the claim language of referring the subject for diagnostic anesthesia. This claim language, under the broadest, reasonable interpretation, encompasses subject matter that may be performed by a human using mental steps or with pen and paper that can involve basic critical thinking, which are types of activities that have been found by the courts to represents abstract ideas (i.e., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). The claim language also meets prong 2 of the step 2A analysis because the above-recited claim language does not integrate the abstract idea into a practical application. That is, there appears to be no tangible improvement in a technology, effect of a particular treatment or prophylaxis, a particular machine or manufacture that is integrated, or transformation/reduction of a particular article to a different state or thing as a result of this claimed subject matter. As a result, step 2A is satisfied and the second step, step 2B, must be considered.
With regard to the second step, the claim does not appear to recite additional elements that amount to significantly more. The additional elements are providing the identified subject with a treatment. However, these elements are not “significantly more” because they are well-known, routine, and/or conventional, as the concept of “providing”, via an unspecified manner, an unidentified “treatment” to someone which could potentially benefit from that unidentified treatment, in the absence of any specificity as to what the treatment might be, what might be involved in providing that treatment, or how a desired effect would be achieved, is merely the concept underlaying the entire field of medicine. Therefore, these elements do not add significantly more and thus the claim as a whole does not amount to significantly more than a judicial exception.
Additionally, the ordered combination of elements do not add anything significantly more to the claimed subject matter. Specifically, the ordered combination of elements do not have any function that is not already supplied by each element individually. That is, the whole is not greater than the sum of its parts.
In view of the above, independent claim 1 fails to recite patent-eligible subject matter under 35 U.S.C. 101. Dependent claim(s) 2-10 fail to cure the deficiencies of independent claim 1 by merely reciting additional abstract ideas or further limitations on abstract ideas already recited. Claims 2-6 describe inherent characteristics of the subject; claim 7 is directed to the insignificant extrasolution activity of data gathering; claims 8-10 ostensibly recite treatments which, per step 2A.2, are still insufficiently particular in their actual treatment or how it relates to the abstract idea to be considered particular treatments providing a practical application of the abstract idea itself. Thus, claim(s) 1-10 is/are rejected under 35 U.S.C. 101.
Claim(s) 14 is/are rejected under 35 U.S.C. 101 because the claimed invention, considering all claim elements both individually and in combination as a whole, do not amount to significantly more than a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea).
Claim 14 is a claim to a process, machine, manufacture, or composition of matter and therefore meets one of the categorical limitations of 35 U.S.C. 101. However, claim 14 meets the first prong of the step 2A analysis because it is directed to a/an abstract idea, as evidenced by the claim language of “providing said subject with a treatment”. This claim language, under the broadest, reasonable interpretation, encompasses subject matter that may be performed by a human using mental steps or with pen and paper that can involve basic critical thinking, which are types of activities that have been found by the courts to represents abstract ideas (i.e., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). The claim language also meets prong 2 of the step 2A analysis because the above-recited claim language does not integrate the abstract idea into a practical application. That is, there appears to be no tangible improvement in a technology, effect of a particular treatment or prophylaxis, a particular machine or manufacture that is integrated, or transformation/reduction of a particular article to a different state or thing as a result of this claimed subject matter. The recited “treatment” is merely set forth at a high level of generality with no clear identification of what the treatment is or how it is provided and no indication of what effect such treatment might generate, such that it does not constitute a particular treatment. As a result, step 2A is satisfied and the second step, step 2B, must be considered.
With regard to the second step, the claim does not appear to recite additional elements that amount to significantly more. No additional elements are included in the claim. Therefore, these elements do not add significantly more and thus the claim as a whole does not amount to significantly more than a judicial exception.
Additionally, the ordered combination of elements do not add anything significantly more to the claimed subject matter. Specifically, the ordered combination of elements do not have any function that is not already supplied by each element individually. That is, the whole is not greater than the sum of its parts.
In view of the above, independent claim 14 fails to recite patent-eligible subject matter under 35 U.S.C. 101. Thus, claim(s) 14 is/are rejected under 35 U.S.C. 101.
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.
Claim(s) 1-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Stoiljkovic (TREM2 Deficiency Disrupts Network Oscillations Leading to Epileptic Activity and Aggravates Amyloid-β-Related Hippocampal Pathophysiology in Mice; Milan Stoiljkovic, Karel Otero Gutierrez, Craig Kelley, Tamas L. Horvath, et al., Journal of Alzheimer's Disease, Sage Publications, 2022-08-02, First published online June 8, 2021) in view of Gonen (US 2019/0269644).
Regarding claim 1, Stoiljkovic discloses a method of identifying a subject in a process of developing Alzheimer's disease (AD) or mild cognitive impairment (MCI), said method comprising:
referring the subject for diagnostic anesthesia during which the presence of epileptiform spikes in the brain of said subject is detected (Methods: Neurophysiological recordings), thereby identifying the subject as being in the process of developing AD or MCI, wherein said subject does not present clinical symptoms associated with AD or MCI (Methods: Mice).
Stoiljkovic does not further disclose providing the identified subject with a treatment capable of attenuating or reducing cortico- hippocampal hyperactivity, thereby delaying the onset of symptoms of said AD or MCI. Gonen teaches providing a subject identified as being in the process of developing AD or MCI after detecting epileptiform spikes in the brain during diagnostic anesthesia (paragraph [0085]) with a treatment capable of attenuating or reducing cortico- hippocampal hyperactivity, thereby delaying the onset of symptoms of said AD or MCI (paragraphs [0007], [0051]-[0052]). It would have been obvious to one of ordinary skill in the art at the time the invention was filed to have followed Stoiljkovic and provided the subject with treatment, as taught by Gonen, in order to prevent the subject’s condition from progressing.
Regarding claim 2, Stoiljkovic further discloses that said subject is about to undergo general anesthesia (Methods: Neurophysiological recordings).
Regarding claims 3 and 4, Stoiljkovic further discloses that said subject is at risk for developing AD or MCI by having a genetic predisposition to and/or a family history of AD or MCI (Methods: Mice).
Regarding claim 5, Stoiljkovic further discloses that said epileptiform spikes are detected at the hippocampus (Results: Epileptiform brain activity).
Regarding claim 6, Stoiljkovic further discloses that said epileptiform spikes are detected at the CA1 or at the medial prefrontal cortex (mPFC) (Methods: Neurophysiological recordings).
Regarding claim 7, Stoiljkovic further discloses that detecting the presence of said epileptiform spikes in the brain of said subject during diagnostic anesthesia is performed by electroencephalogram (EEG), functional magnetic resonance imaging (fMRI), positron emission tomography (PET) scan, and/or magnetoencephalography (MEG) (Methods: Neurophysiological recordings).
Regarding claims 8 and 9, Gonen further teaches that said treatment capable of attenuating or reducing cortico-hippocampal hyperactivity is selected from the group consisting of administration of an active agent capable of reducing dihydroorotate dehydrogenase (DHODH) enzyme activity in the central nervous system (CNS), where the agent is a nucleic acid molecule or a “small” molecule (paragraph [0007]). It would have been obvious to one of ordinary skill in the art at the time the invention was filed to have followed Stoiljkovic as modified by Gonen above, where the treatment comprises providing a “small” molecule agent capable of reducing DHODH enzyme activity, as further taught by Gonen, in order to prevent disease progression.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gonen in view of Stoiljkovic
Regarding claim 14, Gonen discloses a method for reducing likelihood of or delaying the onset of clinical symptoms of Alzheimer's disease (AD) or mild cognitive impairment (MCI) in a subject in need thereof, the subject having been identified as presenting epileptiform spikes in the brain during diagnostic anesthesia, indicating that said subject is in a process of developing said AD or MCI (paragraph [0085]), wherein said method comprises providing said subject with a treatment capable of attenuating or reducing cortico- hippocampal hyperactivity, thereby reducing likelihood of or delaying the onset of clinical symptoms associated with said AD or MCI (paragraphs [0007], [0051]-[0052]). Gonen does not disclose that the subject does not present clinical symptoms associated with said AD or MCI. Stoiljkovic teaches a method for identifying a subject in need of reducing likelihood of or delaying the onset of clinical symptoms of Alzheimer's disease (AD) or mild cognitive impairment (MCI), wherein said subject does not present clinical symptoms associated with said AD or MCI (Methods: Mice), and has been identified as presenting epileptiform spikes in the brain during diagnostic anesthesia, indicating that said subject is in a process of developing said AD or MCI (Methods: Neurophysiological recordings). It would have been obvious to one of ordinary skill in the art at the time the invention was filed to have followed the method of Gonen using a subject not presenting clinical symptoms, as taught by Stoiljkovic, in order to allow delivery of treatment at the earliest possible stage of disease.
Claim(s) 1-8 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Stoiljkovic in view of Fontaine (Denys Fontaine, Serena Santucci, Chapter Four - Deep brain stimulation in Alzheimer's disease, Editor(s): Elena Moro, Mircea Polosan, Clement Hamani, International Review of Neurobiology, Academic Press, Volume 159, 2021, Pages 69-87, ISSN 0074-7742, ISBN 9780128222980, https://doi.org/10.1016/bs.irn.2021.06.005).
Regarding claim 1, Stoiljkovic discloses a method of identifying a subject in a process of developing Alzheimer's disease (AD) or mild cognitive impairment (MCI), said method comprising:
referring the subject for diagnostic anesthesia during which the presence of epileptiform spikes in the brain of said subject is detected (Methods: Neurophysiological recordings), thereby identifying the subject as being in the process of developing AD or MCI, wherein said subject does not present clinical symptoms associated with AD or MCI (Methods: Mice).
Stoiljkovic does not further disclose providing the identified subject with a treatment capable of attenuating or reducing cortico- hippocampal hyperactivity, thereby delaying the onset of symptoms of said AD or MCI. Fontaine teaches providing a subject identified as being in the process of developing AD or MCI after detecting epileptiform spikes in the brain during diagnostic anesthesia (paragraph [0085]) with a treatment capable of attenuating or reducing cortico- hippocampal hyperactivity, thereby delaying the onset of symptoms of said AD or MCI (4. Deep brain stimulation in patients with cognitive impairment). It would have been obvious to one of ordinary skill in the art at the time the invention was filed to have followed Stoiljkovic and provided the subject with treatment, as taught by Fontaine, in order to prevent the subject’s condition from progressing.
Regarding claim 2, Stoiljkovic further discloses that said subject is about to undergo general anesthesia (Methods: Neurophysiological recordings).
Regarding claims 3 and 4, Stoiljkovic further discloses that said subject is at risk for developing AD or MCI by having a genetic predisposition to and/or a family history of AD or MCI (Methods: Mice).
Regarding claim 5, Stoiljkovic further discloses that said epileptiform spikes are detected at the hippocampus (Results: Epileptiform brain activity).
Regarding claim 6, Stoiljkovic further discloses that said epileptiform spikes are detected at the CA1 or at the medial prefrontal cortex (mPFC) (Methods: Neurophysiological recordings).
Regarding claim 7, Stoiljkovic further discloses that detecting the presence of said epileptiform spikes in the brain of said subject during diagnostic anesthesia is performed by electroencephalogram (EEG), functional magnetic resonance imaging (fMRI), positron emission tomography (PET) scan, and/or magnetoencephalography (MEG) (Methods: Neurophysiological recordings).
Regarding claims 8 and 10, Fontaine further teaches that said treatment capable of attenuating or reducing cortico-hippocampal hyperactivity is DBS and said DBS is applied to the thalamic nucleus reuniens (nRE), and/or said DBS is tonic DBS (5.2. Hippocampal neurogenesis). It would have been obvious to one of ordinary skill in the art at the time the invention was filed to have followed Stoiljkovic, as modified by Fontaine, with the treatment being tonic DBS, as further taught by Fontaine, in order to affect memory networks in the subject.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fontaine in view of Stoiljkovic.
Regarding claim 14, Fontaine discloses a method for reducing likelihood of or delaying the onset of clinical symptoms of Alzheimer's disease (AD) or mild cognitive impairment (MCI) in a subject in need thereof, wherein said method comprises providing said subject with a treatment capable of attenuating or reducing cortico- hippocampal hyperactivity, thereby reducing likelihood of or delaying the onset of clinical symptoms associated with said AD or MCI (4. Deep brain stimulation in patients with cognitive impairment). Fontaine does not disclose that the subject does not present clinical symptoms associated with said AD or MCI and has been identified as presenting epileptiform spikes in the brain during diagnostic anesthesia, indicating that said subject is in a process of developing said AD or MCI. Stoiljkovic teaches a method for identifying a subject in need of reducing likelihood of or delaying the onset of clinical symptoms of Alzheimer's disease (AD) or mild cognitive impairment (MCI), wherein said subject does not present clinical symptoms associated with said AD or MCI (Methods: Mice), and has been identified as presenting epileptiform spikes in the brain during diagnostic anesthesia, indicating that said subject is in a process of developing said AD or MCI (Methods: Neurophysiological recordings). It would have been obvious to one of ordinary skill in the art at the time the invention was filed to have followed the method of Fontaine using a subject not presenting clinical symptoms and identified as presenting epileptiform spikes during diagnostic anesthesia, as taught by Stoiljkovic, in order to allow delivery of treatment at the earliest possible stage of disease.
Conclusion
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/KAREN E TOTH/ Examiner, Art Unit 3791
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