DETAILED ACTION
In application filed on 06/22/2022, Claims 1-9 and 16-25 are pending. The claim set submitted on 08/20/2025 is considered because this is the most recent claim set with some preliminary amendments. Claims 8-9, 16-18 and 23-25 are considered in the current office action.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/02/2024, 05/22/2024 and 06/02/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on 08/20/2025 is acknowledged. Claims 1-7 and 19-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/20/2025.
Group II, Claims 8-9, 16-18 and 23-25 are considered on the merits below.
Drawings
The drawings are objected to because certain reference characters in figures, including Figures 9 and 11 are not quite legible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites “the therapy” in line 13 of the Claim. It appears that this limitation should be recited as “the therapy for dementia”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
Claim 16 is 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 16 recites the limitation "the sample" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Is the applicant referring to “a first sample” or “a second sample” in Claim 8?
Applicant should provide clarification.
For the purpose of expedited prosecution, the limitation "the sample" is interpreted by the Examiner as "the first sample and the second sample".
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 8-9, 16-18 and 23-25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation. All claims are directed to statutory categories, i.e., a method (Claims 8-9, 16-18 and 23-25) (Step 1: YES).
Analysis:
Claim 8: Ineligible.
Claim 8 recites a method for monitoring the progress and/or prognosis of a therapy for dementia. Thus, the claim is directed to a method, which is one of the statutory categories of invention (Step 1: YES).
Claim 8 recites “determining the progress of the therapy based on a comparison of the concentrations measured in steps b and d”. Therefore, the claim is directed towards an abstract idea, and more specifically to the abstract idea group of a math or mental process since claim 8 relates to using a math or mental process to “determine the progress of the therapy based on a comparison of the concentrations measured in steps b and d”. (Step 2A, Prong 1: YES).
Step 2A, Prong 2:
This judicial exception is not integrated into a practical application.
Once the evaluation is made then no action is taken, so no particular practical application.
In addition, it appears that “that measuring step is data gathering and an insignificant extra solution activity. See MPEP 2106.05(g).(Step 2A, Prong 2: NO).
Step 2B:
Furthermore, the courts have found that limitations adding insignificant extrasolution activity to the judicial exception, such as mere data gathering in conjunction with a law of nature or abstract idea, are limitations found not to be enough to qualify as ‘significantly more’ when recited in a claim with a judicial exception (see the 2014 Interim Guidance on Patent Subject Matter Eligibility of the Federal Register dated December 16, 2014; and MPEP 2106.05(I)(A)). Note that mere data gathering is not significantly more than the abstract idea. See MPEP 2106.05(g).
Here, there are no additional elements which are significantly more than the abstract idea in independent Claim 8. The limitation of “a) receiving a first sample from a subject at a first timepoint; b) measuring a concentration of NNN-trimethyl-5-aminovalerate, a precursor of NNN- trimethyl-5-aminovalerate, a metabolite of NNN-trimethyl-5-aminovalerate, or a combination thereof in the first sample; c) receiving a second sample from the subject at a second timepoint; d) measuring a concentration of NNN-trimethyl-5-aminovalerate, a precursor of NNN- trimethyl-5-aminovalerate, a metabolite of NNN-trimethyl-5-aminovalerate, or a combination thereof in the second sample”, appear well-understood, routine, and conventional (WURC) in the field of clinical diagnostics, as evidenced by any Rai et al. (US20180003723A1).(Step 2B: NO).
Therefore, Claim 8 is ineligible.
Moreover, Claims 9, 16-18 and 23-25 are rejected by virtue of dependency on Claim 9.
Claim 9, 16-18 and 23-25: Ineligible.
Step 2A, Prong One and Prong Two: Claims 9, 16-18 and 23-25 further define the data gathering steps which appear to be generic and WURC.
Step 2B: The claims do not recite any elements which are significantly more.
Therefore, Claims 9, 16-18 and 23-25 are ineligible.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 8, 16 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over by Rai et al. (US20180003723A1).
Regarding Claim 8, Rai teaches a method for monitoring the progress and/or prognosis of a therapy for sleep disorders associated with neurological disorders including dementia, , the method comprising:
a) receiving a first sample (‘a first saliva sample’) from a subject (See Para 0012… a first saliva sample from an individual diagnosed with the sleep disorder) at a first timepoint (See Para 0008…the individual being tested taken at an earlier time point in the treatment of the sleep disorder);
b) measuring a concentration of NNN-trimethyl-5-aminovalerate, a precursor of NNN- trimethyl-5-aminovalerate, a metabolite of NNN-trimethyl-5-aminovalerate, or a combination thereof (See Para 0029…measuring the levels of biomarkers in a biomarker panel and correlating the measurement with the disease; See Para 0007, 0016…where biomarkers include 5-aminovalerate ( which is a precursor of NNN-trimethyl-5-aminovalerate, as defined in the instant specification [ Page 4]); Also See Para 0018…“measuring”… refers to a quantitative or qualitative determination of the amount or concentration of the biomarker in a particular sample”) in the first sample (See Para 0008…biomarkers in the bodily fluid of the individual being tested taken at an earlier time point in the treatment of the sleep disorder, thereby teaching “first sample”);
c) receiving a second sample from the subject at a second timepoint (See Claim 9…collecting a second saliva sample from the individual diagnosed with the sleep disorder at a time point after the treatment for the sleep disorder has begun);
d) measuring a concentration of NNN-trimethyl-5-aminovalerate, a precursor of NNN- trimethyl-5-aminovalerate, a metabolite of NNN-trimethyl-5-aminovalerate, or a combination thereof (See Para 0029…measuring the levels of biomarkers in a biomarker panel and correlating the measurement with the disease; See Para 0007, 0016…where biomarkers include 5-aminovalerate (which is a precursor of NNN-trimethyl-5-aminovalerate as defined in the instant specification [ Page 4]); Also See Para 0018…“measuring”… refers to a quantitative or qualitative determination of the amount or concentration of the biomarker in a particular sample”) in the second sample (See Claim 9, collecting a second saliva sample, thereby teaching “the second sample”); and
e) determining the progress of the therapy based on a comparison (‘altered favorably’) of the concentrations measured in steps b and d (See Para 0009…the individual is determined to be responding to treatment for the sleep disorder if the relative amounts of the biomarkers in the biological sample have altered favorably from the biomarker levels in a biological sample taken at an earlier first time point from the same individual; i.e. trend towards normal biomarker levels; Also See Para 0044).
While Rai does not explicitly teach a method including single embodiment for monitoring the progress and/or prognosis of a therapy for dementia, Rai does teach that the method is used to diagnose and treat a subject having a sleep disorder associated with dementia (Para 0026).
Since the method of Rai for monitoring sleep disorder associated with dementia include the necessary steps that to monitor dementia,
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the teachings of Rai to include the method for monitoring the progress and/or prognosis of a therapy for dementia, as taught by Rai for the benefit of using a non-invasive means to diagnose and treat a subject with a psychiatric condition (Rai, Para 0026) thus using a single existing therapy to treat a different medical condition. Doing so offers benefits such as reduced costs and shorter therapy/drug development times.
Regarding Claim 16, Rai teaches that the sample is selected from a saliva sample, a urine sample, a blood sample, a serum sample, a sample of brain liquor, a sample of ventricular fluid, a sample of spinal fluid, a brain tissue sample, a microbial sample, a fecal sample, or a stool sample (See Para 0006…the methods and kits described herein include the identification of biomarkers such as proteins in a biological fluid, such as saliva.).
Regarding Claim 23, Rai teaches that wherein in steps b and d, the precursor is 5-aminovalerate or N -trimethyllysine (N(6),N(6),N(6)-trimethyl-L-lysine). (See Para 0007, 0016…where biomarkers include 5-aminovalerate (which is a precursor of NNN-trimethyl-5-aminovalerate as defined in the instant specification [ Page 4]); The claimed “or N -trimethyllysine (N(6),N(6),N(6)-trimethyl-L-lysine)" is interpreted as optional by Examiner).
Claims 9, 17 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Rai et al. (US20180003723A1) as applied to claim 8 above, and further in view of Umek et al. (US20170234892A1).
Regarding Claim 9, While Rai teaches that sample analysis may compare levels in the same individual at different time points during their treatment (Para 0043), Rai does not explicitly teach that the first and second time points are separated by about 3-6 months.
In the analogous art of assay methods, modules and kits useful in the detection, treatment and/or prevention of dementia and related conditions, including but not limited to Alzheimer's disease and mild cognitive disorders, Umek teaches that the first and second time points (See Para 0024… disease progression is monitored over time by monitoring biomarker levels at a first time point, t, and repeating that measurement at a second time point, t+n,) are separated over the span of hours, days, months, and/or years (See Para 0024… The time interval can be measured over the span of hours, days, months, and/or years.)
Further, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design of clinical trials/studies, sample collection at several time points, also known as serial or longitudinal sampling, is a critical technique in biomarker analysis for understanding biological changes over time. Thus, the first and second time points being separated by about 3-6 months is a result effective variable.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Rai to incorporate that the first and second time points are separated by about 3-6 months, as taught Umek for the benefit of assessing the relative change in the biomarker(s) levels in the patient over a given time interval (Umek, Para 0024), allowing for the provision of assays that are useful in the diagnosis, treatment and/or prevention of a disease or condition associated with an abnormal level of one or more isoforms of amyloid beta peptides (“Aβ”) and/or with a changed ratio of levels of Aβ isoforms and/or with the formation of plaques containing one or more Aβ isoforms in a mammal (Umek, Para 0002).
Regarding Claim 17, Rai does not teach that the dementia is selected from Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal dementia, amyotrophic lateral sclerosis, multiple sclerosis, glaucoma, myotonic dystrophy, progressive supranuclear palsy, spinal muscular atrophy, multi-system atrophy, an ataxia, or vascular dementia.
In the analogous art of assay methods, modules and kits useful in the detection, treatment and/or prevention of dementia and related conditions, including but not limited to Alzheimer's disease and mild cognitive disorders, Umek teaches that the dementia is selected from Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal dementia, amyotrophic lateral sclerosis, multiple sclerosis, glaucoma, myotonic dystrophy, progressive supranuclear palsy, spinal muscular atrophy, multi-system atrophy, an ataxia, or vascular dementia (See Para 0014…. Alzheimer's disease is one form of dementia).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Rai to incorporate that the dementia is selected from Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal dementia, amyotrophic lateral sclerosis, multiple sclerosis, glaucoma, myotonic dystrophy, progressive supranuclear palsy, spinal muscular atrophy, multi-system atrophy, an ataxia, or vascular dementia, as taught Umek for the benefit of providing a method for diagnosing Alzheimer's-related dementia and/or plaque formation in the brain of a patient (Umek, Para 0021), allowing for the provision of assays that are useful in the diagnosis, treatment and/or prevention of a disease or condition associated with an abnormal level of one or more isoforms of amyloid beta peptides (“Aβ”) and/or with a changed ratio of levels of Aβ isoforms and/or with the formation of plaques containing one or more Aβ isoforms in a mammal (Umek, Para 0002).
Regarding Claim 25, Rai does not teach that the dementia is Alzheimer's disease.
In the analogous art of assay methods, modules and kits useful in the detection, treatment and/or prevention of dementia and related conditions, including but not limited to Alzheimer's disease and mild cognitive disorders, Umek teaches that the dementia is Alzheimer's disease. (See Para 0014…. Alzheimer's disease is one form of dementia).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Rai to incorporate that the dementia is Alzheimer's disease, as taught Umek for the benefit of providing a method for diagnosing Alzheimer's-related dementia and/or plaque formation in the brain of a patient (Umek, Para 0021), allowing for the provision of assays that are useful in the diagnosis, treatment and/or prevention of a disease or condition associated with an abnormal level of one or more isoforms of amyloid beta peptides (“Aβ”) and/or with a changed ratio of levels of Aβ isoforms and/or with the formation of plaques containing one or more Aβ isoforms in a mammal (Umek, Para 0002).
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Rai et al. (US20180003723A1) as applied to claim 8 above, and further in view of Svetlov et al. (US20130029859A1).
Regarding Claim 18, Rai teaches that the concentration (See Para 0017, 0039… Concentration” or “level”) is measured (See Para 0039…qualitative or quantitative measurement of levels of sleepiness and/or sleep disorder biomarkers in a biological sample such as saliva) with a sensor or by an imaging method (See Para 0039…The biomarkers in a bodily fluid which are used herein to predict, diagnose, or monitor sleepiness can generally be measured and detected through a variety of assays including biosensors. The limitation “or by an imaging method” is interpreted “optional”).
Rai does not teach that the concentration is measured in vivo with a sensor or by an imaging method.
In the analogous art of a process and assay for determining the neurological condition in a subject whereby the level of one or more neuroactive biomarkers is measured in a sample obtained from the subject, Svetlov teaches that the concentration (See Para 0081… The quantity of expression of one or more other neuroactive biomarkers in a sample) is measured in vivo (See Para 0081… detect one or more neuroactive biomarkers in a biological sample in vitro, as well as in vivo) with a sensor or by an imaging method (See Para 0081… Also, in vivo techniques for detection of a marker illustratively include introducing a labeled agent that specifically binds the marker into a biological sample or test subject. For example, the agent can be labeled with a radioactive marker whose presence and location in a biological sample or test subject can be detected by standard imaging techniques.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Rai to incorporate that the concentration is measured in vivo with a sensor or by an imaging method, as taught Svetlov for the benefit of demonstrating that the invention which is means of detecting neurological trauma or condition predictive or indicative of future disease or present or future injury, has utility as a safety or efficacy screening protocol in vivo or in vitro for drug discovery or development (Svetlov, Para 0054), allowing for the provision of a process and an assay for providing improved measurement of neurological conditions (Svetlov, Para 0008), such as neurological damage due to injury, disease, contact with a compound, or other source (Svetlov, Abstract).
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Rai et al. (US20180003723A1) as applied to claim 8 above, and further in view of Fryar-Williams (US20140113318A1).
Regarding Claim 24, Rai does not teach that in steps b and d, the metabolite is glutaric acid or 5-(galactosyl hydroxy)-L-lysine.
In the analogous art of methods for predicting the susceptibility of a subject to a mental or neurodegenerative disorders not limited to Parkinson's disease, motor neurone disease, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and other dementia disorders and glaucoma, Fryar-Williams teaches in steps b and d, the metabolite is glutaric acid or 5-(galactosyl hydroxy)-L-lysine ( See Para 0106…the biomarkers include glutaric acid; In addition, where Glutaric acid is a metabolite of NNN-trimethyl-5-aminovalerate in steps b and d as defined in the instant specification [Page 4]).
Further, Examiner interprets the limitation “or 5-(galactosyl hydroxy)-L-lysine” as optional and thus not required by the Claim.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Rai to incorporate that in steps b and d, the metabolite is glutaric acid or 5-(galactosyl hydroxy)-L-lysine, as taught by Fryar-Williams for the benefit of using one or more additional biomarkers to aid in the diagnosis, prediction, or other assessment of a mental or neurodegenerative disorder. Such additional biomarkers may, for example, be used to validate or extend diagnoses, predictions or assessments made in accordance with the present disclosure, further predict or assess disability or severity, or predict or assess whether the subject tested suffers from any other underlying disorder that may further impact on mental or neurodegenerative disorder diagnosis (Fryar-Williams, Para 0106), allows for the provision of improved methods for prediction of susceptibility to, and diagnosis of, mental and neurodegenerative disorders and for the improved determination and monitoring of treatments for such disorders to improve disease management and ensure that patients receive the most efficacious treatment (Fryar-Williams, Para 0007).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OYELEYE ALEXANDER ALABI whose telephone number is (571)272-1678. The examiner can normally be reached on M-F 7:30am-5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached on (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797