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 .
DETAILED ACTION
Status of the Claims
Claims 1-18 are pending. Claims 1-3, 10 and 17-18 are the subject of this FINAL Office Action. New claim 16 is withdrawn as unelected species of claim 4, previously withdrawn.
Note on Data In Spec/Drawings
Much of the data found in the drawings is impossible to decipher due to the use
of "gray" and "black" lines, and other drawings which are indistinguishable without color
drawings (e.g. Figs. 5B, 5C & 24A).
New Grounds of Rejection - 35 USC § 112(d) – Failure to Further Limit/Improper Dependent Claim
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 17 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 1 already requires saliva samples, which are inherently non-invasive as recited in claim 17; thus claim 17 fails to further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
New Grounds of Rejections - 35 USC § 112- Indefiniteness
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.
Claim 1-3, 10 and 17-18 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 pre-AIA the applicant regards as the invention.
Claim 1 is inconsistent and confusing. First, it states “[m]ethod of adapting based on assessing the circadian rhythm or circadian profile of a subject and/or assessing and predicting the athletic performance of said subject,” then it requires “adapting by changing the subject's timing of physical training, recovery, sleep, light exposure, meals timing, or administration of a supplement based on the assessed circadian rhythm and/or predicted diurnal athletic performance times.” In other words, claim 1 never recites an active step of “assessing and predicting the athletic performance of said subject.” Thus, it is unclear if claim 1 actually requires such a step.
Claim Rejections - 35 USC § 103 - Maintained
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) 1-3 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over NAKGAWA (US20100291553), in view of Winget et al, Circadian rhythms and athletic performance, Med Sci Sports Exerc. 1985 Oct;17(5):498-516, Wolff et al, Exercise Timing and Circadian Rhythms, Curr Opin Physiol. 2019 Apr 27;10:64–69. doi: 10.1016/j.cophys.2019.04.020 and KASAJIMA (US20160206642).
The prior art as a whole demonstrates that it would have been obvious to a skilled artisan at the time of filing to detect Bmal1 and PER2 expression, including in saliva, to determine circadian rhythm abnormalities, which are known to be associated with poor athletic performance with a reasonable expectation of success.
As to claims 1-3 and 10, and detecting and tracking a time course (i.e. three or more time course samples) of BMAL1 and PER2 gene or protein expression to detect circadian rhythms, which is known to affect athletic performance, and using this information to adjust timing of eating, sleeping, exercise, nutrient ingestion and other body adjustments to achieve better health, all of this is incredibly well-known. For example, NAKAGAWA reflects the state of the art: “To cite a familiar example [of defect or diversity in function or gene of a biomolecule involved in a biological clock are causative factors of lifestyle-related diseases], it is known that the mind and body activity and exercise performance also have a circadian rhythm, and a rhythm which maximizes one's own ability, a rhythm which is good for learning or training, an eating rhythm which makes the body weight to increase easily, and the like are considered” (para. 0130). To this end, NAKAGAWA teaches to detect expression variation of BMAL1-CLOCK and PER2 genes at 2.5-hour intervals, or 4-hour intervals using qPCR (paras. 0133-35; see also para. 0137; Figs. 23-24). This allows one to fit the expression levels to a periodic 24-hour cycle to determine circadian rhythm of the subject (id.). In other words, although NAKAGAWA does not explicitly teach assessing and predicting the individual diurnal athletic performance times, both for strength exercises and endurance exercises and then adapting by changing the timing of physical training, recovery, sleep, light exposure, meals timing, or administration of a supplement based on the assessed circadian rhythm and/or predicted diurnal athletic performance times, yet this is strongly suggested by NAKAGAWA, and is incredibly familiar in the circadian rhythm art.
In fact, this suggestion has existed for decades. For example, Winget, in 1985, explained that “[d]aily or circadian rhythmical oscillations occur in several physiological and behavioral functions that contribute to athletic performance. . . . Factors influencing the degree of impairment and duration of readaptation include direction of flight, rhythm synchronizer intensity, dietary constituents and timing of meals, and individual factors such as morningness/eveningness, personality traits, and motivation. It is the intent of the authors to increase awareness of circadian rhythmic influences upon physiology and performance and to provide a scientific data base for the human circadian system so that coaches and athletes can make reasonable decisions to reduce the negative impact of jet-lag and facilitate readaptation following transmeridian travel” (Abstract). More recently, as summarized in Wolff, “the outcomes of exercise may be modified depending on when exercise is performed” (Abstract). Wolff even acknowledges the role of the core molecular clock (which includes BMAL, CLOCK, PER2, etc.) in maintaining circadian rhythms, and its cyclical expression (pgs. 2-3; Fig. 1). Wolff proceeds to explain how this circadian oscillation of the core clock gene expression affects exercise:
Because exercise is a major physiological perturbation, the circadian oscillation of basal physiological rhythms has a direct effect on exercise responses. Several studies in humans and rodents have revealed that variables such as skeletal muscle strength and oxidative capacity demonstrate significant differences over time of day [19–22]. For example, studies have consistently demonstrated increased strength in the later afternoon versus morning [19] while oxidative capacity peaks in the late evening [22]. In addition, basal systemic hormone and metabolite concentrations oscillate over a 24h period, although the impact of these oscillation on exercise are unclear [20,22–25]. It is clear, however, that exercise at different times of day leads to different outcomes [19,25–27]. One recent example was provided by Dalbram and colleagues who reported that exercise in the late active phase of mice reduced the accumulation of body mass during high-fat diet compared to exercise in the early active phase [28]. The effect of circadian timing on an integrative outcome, such as weight gain, is exciting and will provide important considerations for future interventions. Additionally, future studies in both human and rodent interventions must take care to provide transparent reporting of circadian conditions (e.g., light/dark cycles, feeding status), as well as robust time of day sampling rates. Attention to these details are critical to help distinguish intrinsic circadian related changes vs. environmental/behavior effects [29]. We also suggest cautious assessments of experimental circadian controls prior to sweeping conclusions regarding the outcomes of an intervention.
Circadian timing has also been reported to affect exercise outcomes at the molecular level. The molecular responses of muscle to exercise are well-characterized. In particular, the mechanistic target of rapamycin complex 1 (mTORC1) and peroxisome proliferator activated receptor gamma coactivator 1 (PGC1) pathways are widely studied exercise-responsive pathways. Recently, these exercise-stimulated pathways were identified as being downstream of the molecular clock, providing a molecular mechanism through which circadian timing can influence exercise responses [30,31]. For instance, Wu and colleagues reported that PER2 lowers mTORC1 activity [32], and PER2 expression oscillates (peaking at the end of the inactive phase [33]), linking time-of-day to the exercise response. Additionally, morning resistance exercise, but not afternoon exercise in trained individuals lead to the activation of the mTORC1 signaling pathway, as assessed by p70S6K phosphorylation [34]. Despite the influence of circadian timing on hypertrophic signaling following acute resistance exercise, circadian timing of resistance exercise training does not influence skeletal muscle hypertrophy [27,34]. Endurance exercise increases PGC1α, which is a clock-controlled gene in skeletal muscle [35]. Thus, circadian timing may influence the endurance exercise response by modulating the activation PGC1 in skeletal muscle. To our knowledge, no investigations have assessed the impact of circadian timing as a modifier of endurance exercise training responses. However, it is unclear if any human investigation has performed exercise at the onset of the inactive phase (dark), which would closely mirror previous interventions using rodent models [15,36,37].
One approach to test the influence of the circadian clock on exercise outcomes is with genetic models of circadian disruption. In one model of circadian disruption (ClockΔ19), where mice have a 27–28h endogenous period length, mutant mice had a 49% reduction in treadmill exercise duration compared to wild type [38] suggesting that animals with internal clocks out of sync with environmental cues (i.e. misalignment) have reduced exercise capacity. Additionally, in a model of complete circadian disruption, activity levels in mice lacking Bmal1 were severely reduced (~2 fold) compared to wild type animals [39]. Together, these findings suggest that circadian disruption reduces exercise capacity. However, despite reduced exercise capacity in mice with circadian disruption, the animals retain plasticity. Specifically, exercise training restored the exercise capacity of the ClockΔ19 mice, although no studies have examined exercise training in Bmal1 knockout animals. Together, these findings have major therapeutic implications, as circadian disruption has been linked to numerous diseases [24,40,41]. Thus, exercise may reduce mortality through restoring the function of disrupted molecular clocks. Below we highlight the mechanisms through which exercise modulates the molecular clock
(pgs. 3-4). In other words, a skilled artisan would have been familiar with the fact that circadian timing of eating, exercise, sleeping, and ingestion of supplements and other nutrients, as measured by the molecular clock, is important to achieve better health effects. Thus, the prior art is replete with motivation to use circadian rhythm assessment or monitoring via the molecular clock to determine athletic performance, and then adjust eating, exercise, sleeping, and ingestion of supplements and other nutrients to positively effect that performance.
The above prior art does not explicitly teach to use saliva samples.
However, saliva samples were familiar option in the art, regularly used with success to detect gene expression. For example, KASAJIMA teaches that Bmal1 and PER2 can be detected in saliva (para. 0040).
In sum, the prior art demonstrates conclusively that a skilled artisan would have been motivated to detect Bmal1 and PER2 in saliva samples to determine circadian rhythms in subjects, and further determine athletic performance in order to adjust the timing of physical training, recovery, sleep, light exposure, meals timing, or administration of a supplement with a reasonable expectation of success.
The Examiner also notes that he is a skilled artisan in the field of circadian rhythms as demonstrated by the publications found at https://scholar.google.com/citations?user=J47haMEAAAAJ&hl=en. In light of this, the Examiner’s conclusions are also backed by His knowledge in the field.
To put the above another way, a skilled artisan would have expected that both Bmal1 and Per2 expression are cyclical according to circadian rhythms; and that this cyclical nature can be tracked to determine when a subject is at a particular point of a circadian rhythm, or if a rhythm is defective. That skilled artisan would also have known that circadian rhythm timing and defects affect athletic performance, and therefor could make appropriate adjustments. This is all reflected in the fact that Applicants recognize that the prior art teaches that circadian rhythms affect athletic performance (Spec., pgs. 1-5).
What Applicants seem to believe is the invention is the use of non-invasive plasma samples (Spec, pgs. 5-6). However, saliva sample are routinely used in the art. Thus, the Examiner strongly suggests that Applicants provide evidence of unexpected results commensurate in scope with the claims. See MPEP § 716.
Response to Arguments
The rejections are maintained because Applicants’ claims, read as whole, are much broader than their characterization. To start, the claims do not require computational assessment and prediction of individual diurnal athletic performance times, much less any athletic adaptation. Instead, it is merely an option in the claims. This is because the claims state “[m]ethod of adapting based on assessing the circadian rhythm or circadian profile of a subject and/or assessing and predicting the athletic performance of said subject . . . [determining circadian rhythm using clock network gene expression during a time course], assessing and predicting the circadian rhythm of said subject and/or the individual diurnal athletic performance times . . . wherein the computational step comprises processing the determined expression levels and/or the respectively fitted periodic functions to derive characteristic data for each of the at least two genes, and adapting by changing the subject's timing of physical training, recovery, sleep, light exposure, meals timing, or administration of a supplement based on the assessed circadian rhythm and/or predicted diurnal athletic performance times.” Thus, at the least, the claims do not reflect Applicants’ arguments.
For example, Applicants argue that “the cited prior art does not provide actionable assessment and prediction of circadian rhythm and/or individual diurnal athletic performance times, does not enable individualized recommendations, and does not suggest modifying the subject's behavior, such as timing of physical training based on the assessment and prediction” (Reply, pg. 11). However, neither do Applicants’ claims, as explained above. As to any enablement of the prior art, all prior art is presumed enabled; it is Applicants’ duty to prove otherwise. See Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1355 (Fed. Cir. 2003); In re Antor, 689 F.3d 1282, 1287-94 (Fed. Cir. 2012); In re Morsa, 713 F.3d 104, 109-11 (Fed. Cir. 2013).
Remarkably, Applicants argue that “Nakagawa . . . fails to connect any of its mentioned genes (including the briefly referred to BMAL1, PER1, and PER2 in experimental examples) as being relevant to prediction of circadian rhythm” (Reply, pg. 11). As any artisan in this field would immediately understand, these genes are routinely used to asses, determine and predict an individual’s circadian rhythm. In fact, paragraph 0128 gets to this: “Recently, it has gradually been revealed that defect or diversity in function or gene of a biomolecule involved in a biological clock are causative factors of lifestyle-related diseases such as cancer, diabetes, vascular diseases, and neurodegenerative diseases.” As is abundantly clear from the other prior art cited, the biological clock gene expression includes BMAL1 (which interacts with CLOCK), Per1 and Per2. Applicants are trying to attack Nakagawa on its own without any regard to the prior art as a whole, which completely fails. Such specious assertions provide grounds to reduce the weight of Applicants’ arguments.
In fact, as is very clear from the rejections above, Nakagawa was cited to demonstrate the state of the art as a whole. Specifically, that many artisans understood the effect of clock gene expression on individual physiology such as athletic performance, and that circadian rhythms were routinely tracked using clock gene expression over time courses. Applicants simply choose to blind themselves to these arguments and facts drawn from Nakagawa, and characterize the Examiner’s arguments as “Nakagawa somehow ‘strongly suggested’ it” (Reply, pg. 11; emphasis added). Applicants should address the Examiner’s actual arguments reproduced above, and address the analysis of the prior art as whole, not attack each reference individually.
Applicants also oddly argue that Winget and Wolff are irrelevant to the claimed invention because “it is a well-known fallacy to apply macro teachings to micro circumstances” (Reply, pg. 11). Specifically, “[t]he current application goes to great lengths to explain that macro knowledge falls apart when applied to the individual level” (Reply, pgs. 11-12). Applicants’ assert a distinction without a difference. A population is constituted by individuals/subjects, and these are precisely what both Winget and Wolff discuss. For example, Winget states at the Concluding Remarks & Future Directions, “[a]pplying circadian or time of day principles to exercise interventions hold promise for improving the outcomes for exercise for healthy subjects, patient populations as well as elite athletes” (pg. 5; emphases added). In other words, any study of populations is used to apply to individuals. As any skilled artisan with the ability to logic would immediately understand, any exercise intervention would have to applied to an individual, whether part of a larger population or not. Thus, this argument fails from the outset.
Applicants also assert, while ignoring, once again, the Examiner’s assessment of the prior art as a whole, “Winget merely states that athletic performance can vary by time of day and never bridges the gap from the mere physiological observation to individualized molecular diagnostics and actionable predictive intervention” (Reply, pg. 12). Applicants are encouraged to read the rejections again as they address the supposed “gap.”
Applicants also argue that “Wolff confirms that the field was still in an exploratory mode and lacked the claimed predictive framework even at a population level” (Reply, pg. 12). However, so are Applicants’ claims. The claims do not require any particular time course, any particular expression levels of any particular genes, any particular circadian rhythms tied to any particular athletic performance predictions or assessments, or any particular changes to behavior. Instead, the claims encompass the broad concept, just like the prior art, of looking at circadian rhythms assessed of gene expression time courses to generically adapt generic behaviors. This concept is not patentable based on the prior art as a whole.
In another attempt at an individualistic attack on the references cited by the Examiner, Applicants assert Kasajima “addresses a fundamentally different issue, namely modulation of gene expression rather than its use as a predictive biomarker for assessing and predicting the circadian rhythm and/or the individual diurnal athletic performance times and adapting a subject's behavior” (Reply, pg. 13). Once again, Applicants are encouraged to re=read the rejections reproduced above. Those rejections address the well-known fact that saliva samples are routinely used for gene expression, of which “gene expression levels of at least two members of genes associated with a core-clock network” is a routine application.
Next, Applicants pull out the well-worn, but rarely effective attack that the Examiner used hindsight to impermissibly reject the claims. Applicants fail in their burden to demonstrate as much. As explained by MPEP § 2145(X)(A) (emphases added):
Applicants may argue that the examiner’s conclusion of obviousness is based on improper hindsight reasoning. However, “[a]ny judgement on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper.” In re McLaughlin 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971). Applicants may also argue that the combination of two or more references is “hindsight” because “express” motivation to combine the references is lacking. However, there is no requirement that an “express, written motivation to combine must appear in prior art references before a finding of obviousness.” See Ruiz v. A.B. Chance Co., 357 F.3d 1270, 1276, 69 USPQ2d 1686, 1690 (Fed. Cir. 2004). See MPEP § 2141 and § 2143 for guidance regarding establishment of a prima facie case of obviousness.
Here, the Examiner has shown that the “combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results” based on “the teachings of the prior art, taken as a whole.” See KSR Int'l v. Teleflex Inc., 550 U.S. 398, 416 (2007); In re Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991). There is absolutely no reference to the instant specification in order to teach or suggest any element of the claimed invention. Rather, the obviousness case was very clearly built on “only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made.”
Applicants also make a big deal about “translating molecular data based on expression of specific genes for a core clock network into predictive models, and thereby enabling personalized, time-specific adaptation of a subject's behaviour” (Reply, pg. 14). However, the claims, as explained above, never describe any predictive models, much less any specific molecular data, or any specific personalized, time-specific adaptation of a subject's behaviour. The claims broadly recite the well-known concept that circadian rhythms as measured by gene expression time courses are correlated with certain phenotypic and behavioral effects at certain times, which one can use to optimize timing of certain behaviors. There is nothing new about this.
Applicants also make a big deal about the “non-invasive molecular sampling” as an advance in circadian rhythm gene expression analysis. However, as explained above, the use of saliva samples to assess gene expression is routine in the art, for the same exact reason as asserted here, that is for its non-invasiveness.
Finally, we reach the Declaration filed 06/05/2026. Applicants describe Figures 23, 25 and 29 as showing circadian oscillations in saliva-derived gene expression from healthy individuals. This is not inventive, at all. It merely confirms what is known in the art. The prior art as a whole clearly demonstrates that a skilled artisan would expect circadian oscillations in saliva-derived gene expression from clock genes such as CLOCK, BMAL1, PER2, etc.
Applicants state that Figures 30 and 31 show “harmonic regression analyses applied to cortisol measurements and gene expression data using the circadian period predicted from the optimal PER2 fit described in Figure 29.” This is already known: “Cortisol is an essential steroid hormone secreted by the adrenal gland and like many other physiological processes in the body has a circadian rhythm. This rhythm is distinct and is regulated by the main circadian oscillator (pacemaker) in the suprachiasmatic nucleus (SCN) which is located in the hypothalamus” (Chan & Debono, Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy, Ther Adv Endocrinol Metab. 2010 Jun;1(3):129–138. doi: 10.1177/2042018810380214, Abstract; see also Figs 1 & 4). As explained in the section “Central and peripheral circadian oscillators,” the SCN clock genes manage the peripheral (e.g. saliva) clock genes; thus, a skilled artisan would expect cortisol to track with the circadian rhythms of peripheral (e.g. saliva) gene expression.
As to the Nelson 2025 reference, the Malhan 2025 reference and the Basti 2021 reference, Applicants completely fail to demonstrate unexpected evidence commensurate in scope with the claims, much less with any close nexus with the claimed invention. See MPEP § 716. First, Applicants have not explained how these references demonstrate unexpected evidence. On the contrary, these references simply seem to confirm the well-known concept that cortisol is subject to circadian rhythms, saliva can be used for gene expression analysis, and physiological features fluctuate with circadian rhythms. Basti finds that “Core-clock genes show daily fluctuations in expression in all biological samples tested for all participants. Exercise performance peaks in the late afternoon (15–18 hours for both men and women) and shows variations in performance, depending on the type of exercise (eg, strength vs endurance). Muscle tone varies across the day and higher muscle tone correlates with better performance. Molecular daily profiles correlate with daily variation in exercise performance” (Abstract). However, the claims do not require any of these details. In addition, these fluctuations of exercise performance and muscle properties were expected based on the knowledge in the art. See Teo et al, Circadian Rhythms in Exercise Performance: Implications for Hormonal and Muscular Adaptation, J Sports Sci Med. 2011 Dec 1;10(4):600–606; Schroder & Esser, Circadian Rhythms, skeletal muscle molecular clocks and exercise, Exerc Sport Sci Rev. 2013 Oct;41(4):10.1097/JES.0b013e3182a58a70. doi: 10.1097/JES.0b013e3182a58a70; Dollet & Zierath, Interplay between diet, exercise and the molecular circadian clock in orchestrating metabolic adaptations of adipose tissue, J Physiol, 597: 1439-1450. https://doi.org/10.1113/JP276488, 01/07/2019; Aoyama & Shibata, The Role of Circadian Rhythms in Muscular and Osseous Physiology and Their Regulation by Nutrition and Exercise, Front. Neurosci., 13 February 2017, Sec. Neuroendocrine Science, Volume 11 - 2017 | https://doi.org/10.3389/fnins.2017.00063. Basti merely shows that using saliva-based clock gene expression time courses as a proxy for circadian rhythms allows one to track the known rhythms of athletic performance proxies. This was expected based on the prior art as a whole. Applicants have not demonstrated any data that is different in kind from what was expected; rather only expected concepts. It is also noted that Basti re-affirms the Examiner’s conclusions of obviousness:
Given the regulation of cellular processes and subsequent described impact on physiology, the internal clock is thought to have an influence on the athletic performance, and exercising at different times of day results in different outcomes.3 15–23 Several physiological features which influence athletic performance show circadian variation including CBT,16 hormone levels24 and cardiac dynamics (blood pressure and heart rate variability).25 Accordingly, performance improvements were most often observed in the early evening hours.26 The clock affects exercise performance via core-clock genes (eg, CLOCK and BMAL1), which influence the function and structure of skeletal muscles, where the core-clock machinery seems to be closely aligned to metabolic flux.27–31 Also, specific mutations in PER3 correlated with intra-individual variation in athletic performance at different times of day.32 Exercise, on the other hand, can change the clock machinery as well. Indeed, AMPK (adenosine monophosphate-activated protein kinase), a key energy sensor in skeletal muscle, can reduce the stability of CRY1 and PER2 and serves as a circadian time cue.33–35 Though exercise can affect the circadian clock if practised over periods of many years, the extent and duration of this effect relies heavily on the intensity and duration of the exercise as reported for professional athletes.23 36
[ . . . ]
. . . The use of saliva is of particular interest as it is non-invasive, contains white blood cells and epithelial cells and hence provides information on gene expression level.42 43 Saliva content relates to health status44–47 and circadian rhythms for human and murine submandibular salivary glands have been reported.48 49 . . .
(Introduction). Basti only re-affirms this expectation; it does not present any unexpected evidence, much less commensurate in scope with the broad claims. Even more, Basti is speculative:
Thus, the methods reported are appropriate to analyse potential clock dysregulations and may enable us to circumvent them to improve and maintain health. This knowledge can help us to develop preventive measurements to diminish the negative effects of circadian disruption on human physiology and health. Further, it can be used to optimise the timing of exercise leading to increased physical performance or to guide muscle tone and rehabilitation treatment in clinical settings
(id.) Basti fails to present any novel or non-obvious optimization or prevention techniques, or prediction model, much less one commensurate with the broad scope of the claims.
Malhan finds “significant disruptions in circadian rhythms, specifically in the expression of the core clock genes BMAL1 and PER2, following treatment [with rucaparib]” (Abstract). Nothing in the claims requires anything close to this. In other words, the claims are nowhere near commensurate with disruptions in circadian rhythms, specifically in the expression of the core clock genes BMAL1 and PER2, following treatment with rucaparib. Moreover, only one author in Malhan overlaps with the inventors here, and that author is not the primary author or the PI. It is also a 2025 reference; whereas the priority date here is in 2020. This evidences that the Malhan reference is irrelevant to the claimed invention. Similarly, Nelson is a 2025 reference, and only the PI inventor overlaps the inventors here. Thus, the evidence of Malhan, and Nelson and Basti not only fail to demonstrate unexpected results of the claimed invention, moreover, they are not commensurate in scope with the very broad claims.
As to new claim 18, “modifying” is equivalent to “changing”; and sleep, recovery, nutritional intake and light exposure overlap with the same steps in claim 1, which were rejected previously, above.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aaron Priest whose telephone number is (571)270-1095. The examiner can normally be reached 8am-6pm.
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/AARON A PRIEST/ Primary Examiner, Art Unit 1681
Prosecution Insights