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 .
Applicant's amendments and remarks, filed on 09/08/2026, are acknowledged. Applicant's arguments have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn.
Status of Claims
Claims 1, 3-9, 13, 14, 15 are under examination.
Claims 2, 10-12, 16-20 are withdrawn.
Priority
The instant application claims the benefit of priority to U.S. Provisional Application 63/729,267, filed on December 6, 2024.
Withdrawn Rejections
The rejection of claims 1, 3-9, 13, 14, 15 under 35 U.S.C. 101 because the claimed invention is not supported by either a substantial asserted utility or a well-established utility is withdrawn in view of applicant’s amendments.
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.
The following rejection is modified in view of applicant’s amendments.
Claims 1, 3-9, 13, 14, 15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and ‘as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355).
Guidance: Step 1.
Under the broadest reasonable interpretation, the claimed invention (claim 1 being representative) is directed to a system for performing a process and therefore falls within one of the four statutory categories.
A. Guidance Step 2A, Prong 1
The Revised Guidance instructs us first to determine whether any judicial exception to patent eligibility is recited in the claim. The Revised Guidance identifies three judicially-excepted groupings identified by the courts as abstract ideas: (1) mathematical concepts, (2) certain methods of organizing human behavior such as fundamental economic practices, and (3) mental processes. In this case, the following steps encompass an abstract idea for the reasons set forth below:
identify, for a first organ of the plurality of organs of the body of the subject individual and from the plurality of CpG sites, a first subset of the CpG sites by filtering out CpG sites that do not satisfy at least one variability threshold, the first subset of the CpG sites determined to be associated with the first organ based on a variability analysis, wherein the first subset of the CpG sites corresponding to the first organ is different from a second subset of the CpG sites corresponding to a second organ of the body;
analyze longitudinal variations of the DNA methylation levels of first subset of the CpG sites over the time series, wherein the longitudinal variations comprise alterations of DNA methylation levels of the first subset of-CpG sites;
generate an organ-specific biological-age profile characterizing functional organismal aging of the first organ based on analyzing the longitudinal variations;
Mental Processes
With regards to the identify step, this is recited at a high level of generality without any technological details directed to how it is performed. As such, this step encompasses observing and/or analyzing data and can be performed in the mind of a scientist or with a pencil and paper. Therefore, this step encompasses a mental process. MPEP 2106.04(a)(2), section III.
With regards to the analyze and generate steps, these are recited at a high level of generality without any technological details or rules directed to how they are performed. As such, this step encompasses analyzing data and/or manipulating data (to generate additional data) and can be performed in the mind of a scientist or with a pencil and paper. Therefore, this step encompasses a mental process. MPEP 2106.04(a)(2), section III.
Applicant is reminded that the Office's eligibility guidance does not set limit on the number of calculations that can or cannot be performed mentally. MPEP § 2106.04(a)(2)III. Moreover, it is important to note that a claim to “collecting information, analyzing it, and displaying certain results of the collection and analysis,” where the data analysis steps are recited at a high level of generality such that they could practically be performed in the human mind, Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016). [Step 2A, Prong 1: YES].
Mathematical Concept
In addition, the claimed identify step requires filtering data based on a comparison to a threshold value which amounts to a mathematical correlation. It is important to note that a mathematical concept need not be expressed in mathematical symbols, because “[w]ords used in a claim operating on data to solve a problem can serve the same purpose as a formula.” In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). Therefore, this step encompasses a mathematical concept of manipulating information through mathematical correlations or calculations. MPEP 2106.04(a)(2) Section I [Step 2A, Prong 1: YES].
B. Guidance Step 2A, Prong 2
Having made that determination, under the 2019 Guidance, the examiner next determines whether there are additional elements beyond the recited abstract idea(s) that integrate them into a practical application. In this case, the additional steps/elements that are not part of the abstract idea are as follows:
receive discrete time series of methylation profiles, each methylation profile comprising DNA methylation levels at a plurality of CpG sites, the DNA methylation levels measured from a plurality of biological samples of the body of the subject individual over a series of discrete periods;
a user interface in communication with computing system, wherein the user interface is configured to display organ-specific biological-age profiles of at least a subset of organs of the subject individual.
a computing system comprising memory and one or more processors, the memory storing code instructions, wherein the code instructions, when executed by the one or more processors,
With regards to receiving, this step is recited at a high level of generality and results in gathering a particular type of data for use by the abstract idea. Accordingly, this step amounts to insignificant extra-solution activity and are not indicative of an integration into a practical application. See MPEP 2106.05(g). It is noted that product-by-process type limitations directed to the how the data was obtained, per se, have no limiting effect on the method as claimed.
With regards to displaying, this step is recited at a high level of generality and amounts to outputting or displaying data. Accordingly, this step amounts to insignificant extra-solution activity and is not indicative of an integration into a practical application. See MPEP 2106.05(g).
With regards to the additional elements directed to processors, memory, and user interface, these are nothing more than generic computer components being used as a tool to perform generic computer functions or the abstract idea. See MPEP 2106.05(b). In summary, the claimed invention does not provide any objective evidence of an improvement to the technology, nor does the specification explain the details of an unconventional technical solution expressed in the claim, or identify technical improvements realized by the claim over the prior art. See MPEP 2106.04(d)(1) and MPEP 2106.05(a). Therefore, even when viewed in combination, these additional steps/elements do not integrate the recited judicial exception into a practical application. [Step 2A, Prong 2: NO].
C. Guidance Step 2B:
This part of the eligibility analysis evaluates whether the claim as a whole amount to significantly more than the recited exception i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP 2106.05.
As discussed above, the non-abstract steps/elements amount to nothing more than insignificant extra-solution activity. In addition, Bjornsson et al. (JAMA, June 25, 2008, Vol 299, No. 24, pp. 2877-83) teaches a method for determining longitudinal changes in global DNA methylation in individuals, including obtaining methylation data associated with CpG sites and generating time-series methylation profiles [See Abstract, Methods, Figures 1-2, Table 1]. Hannum et al. (Molecular Cell, 2013, 49, pp. 359–367) teaches obtaining methylation profiles of two different cohorts sampled from a mixed population of individuals over a specified age range (i.e. 19 to 101), which reads on time-series methylation data. Samples were taken as whole blood and processed with the Illu mina Infinium Human Methylation 450 BeadChip assay which measures the methylation states of 485,577 CpG markers [page 340, col. 1]. Therefore, even upon reconsideration, there is nothing unconventional with regards to the above non-abstract elements/steps directed to receiving time-series methylation profile associated with CpG sites. See MPEP 2106.05(d)(Part II). Thus, the independent claim(s) as a whole do not amount to significantly more than the exception itself. Therefore, the claim(s) is/are not patent eligible. [Step 2B: NO].
Dependent Claims
Dependent claims 3-9, 13, 14, 15 have also been considered under the two-part analysis but do not include additional steps/elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s) for the following reasons. Regarding claims 3-9, these claims further limit the specificity of the abstract idea or the nature of the data being used and therefore are not patent eligible for reasons set forth above (Step 2A, prong 1). In addition, claims 3, 6, 8 further recite applying a model and calculating scores, which amount to a mathematical concept based on manipulating information through mathematical correlations or calculations. MPEP 2106.04(a)(2) Section I. It is important to note that a mathematical concept need not be expressed in mathematical symbols, because “[w]ords used in a claim operating on data to solve a problem can serve the same purpose as a formula.” In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). See, e.g., SAP America, Inc. v. InvestPic, LLC, 898 F.3d 1161, 1163, 127 USPQ2d 1597, 1599 (Fed. Cir. 2018).
Regarding claim(s) 13, 14, 15, the claims further limit the specificity of what is displayed by the user interface. Accordingly, these steps are not indicative of an integration into a practical application and do not amount to significant more for reasons set forth above (Step 2A, prong 2 analysis, and Step 2B analysis). Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea (and/or natural correlation) without significantly more.
Response to Arguments
Applicant’s arguments, filed 09/08/2026, have been fully considered but are not persuasive for the following reasons.
Applicant argues that the claimed system recites a technological improvement in processing high-dimensional DNA methylation data for organ-specific aging analysis, by providing minimizing storage footprint, reducing system complexity, and optimizing memory and processor usage [0027-0028].
In response, it is noted at the outset that the improvement analysis at Step 2A Prong Two differs in some respects from the improvements analysis at Step 2B. Specifically, the “improvements” analysis in Step 2A determines whether the claim pertains to an improvement to the functioning of a computer or to another technology without reference to what is well-understood, routine, conventional activity. As set forth above, the claimed processors, memory, and user interface, are nothing more than generic computer components being used as a tool to perform generic computer functions or the abstract idea. See MPEP 2106.05(b). Applicant also does not contend that it invented any of the processor or elements or that they were unknown in the art as of time of the invention. Accordingly, the claimed processor, memory, and interface do not result in an improvement to the functioning of a computer or another technology as there is nothing unconventional with regards to the combination of claimed steps. For reasons discussed above, there is also nothing unconventional with regards to the methylation data or how it is being received (Step 2A, prong 2 and Step 2B). The claimed invention merely manipulates existing information to generate additional information, which, without more, is not patent eligible. See Digitech Image Techs., LLC v. Elecs. For Imaging, Inc., 758 F.3d 1344, 1351 (Fed. Cir. 2014) (“Without additional limitations, a process that employs mathematical algorithms to manipulate existing information to generate additional information is not patent eligible.”); see also CyberSource, 654 F.3d at 1375 (“The mere manipulation or reorganization of data…does not satisfy the transformation prong.”).
Applicant additionally argues that the technical improvement is especially significant in the disclosed assay environment. In response, the claim does not positively recite any steps directed to performing a (physical) assay. Therefore, applicant’s argument is not persuasive because it relies upon limitations that are not being claimed. See MPEP § 2145. Moreover, applicant does not provide any objective evidence of an improvement to the technology, nor does the specification explain the details of an unconventional technical solution expressed in the claim, or identify technical improvements realized by the claim over the prior art. See MPEP 2106.04(d)(1) and MPEP 2106.05(a).
Applicant additionally argues that the claims as amended recite a practical application that reduces feature space used for processing. In this case, applicant appears to be arguing that the improvement lies in the abstract idea (since feature space, although not presently claimed, is indeed directed to a mathematical concept). However, this argument is also not persuasive as it is well established that the abstract idea alone cannot supply the inventive concept that renders the invention ‘significantly more’ than that ineligible concept.” BSG Tech LLC v. BuySeasons, Inc., 899 F.3d 1281, 1290 (Fed. Cir. 2018). For at least these reasons, the rejection is maintained.
Claim Rejections - 35 USC § 112a
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
This rejection is necessitated in view of applicant’s amendments.
Claims 1, 3-9, 13, 14, 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim(s) 1, the specification fails to provide written description support for the following steps:
identifying, for a first organ of the plurality of organs of the body of the subject individual and from the plurality of CpG sites, a first subset of the CpG sites by filtering out CpG sites that do not satisfy at least one variability threshold, the first subset of the CpG sites determined to be associated with the first organ based on a variability analysis, wherein the first subset of the CpG sites corresponding to the first organ is different from a second subset of the CpG sites corresponding to a second organ of the body;
analyzing longitudinal variations of the DNA methylation levels of first subset of the CpG sites over the time series, wherein the longitudinal variations comprise alterations of DNA methylation levels of the first subset of-CpG sites;
generating an organ-specific biological-age profile characterizing functional organismal aging of the first organ based on analyzing the longitudinal variations;
With regards said identifying, the instant claims are not limited to any specific CpG sites. As a result, it is unclear how the practitioner would know which CpG sites are markers for aging. One of ordinary skill in the art would recognize that CpG sites are associated with different organs, genes, and/or sequences, for example, and that practicing the claimed invention would require knowledge of specific CpG sites that are associated with age. Similarly, the artisan would also require knowledge of the levels of methylation at specific CpG sites that predict age across multiple tissues. However, a review of the specification does not provide any evidence that applicant had knowledge of specific CpG sites, genes, and/or sequences associated with age (biological or otherwise). A review of the prior art teaches that such limitations are not trivial. For example, Jones et al. (Aging Cell, 2015, 14, pp. 924–932) teaches that age is associated with highly specific CpG sites [Summary and Table 1]. Moreover, Jones teaches that DNA methylation profiles are highly divergent in different tissues, and that comparing DNA methylation across tissues presents many unique challenges. Therefore, the specification does not satisfy the written description requirement with respect to the full scope of CpG sites being claimed. For more information regarding the written description requirement, see MPEP §2161.01- §2163.07(b).
With regards said identifying and generating, the instant claims are not limited to any specific type of variability analysis or variability thresholds and amount to functional language specifying desired results and/or specific functions. As a result, it is unclear how the practitioner would know what type of analysis is being performed and what thresholds are indicative of the desired result. One of ordinary skill in the art would understand that this type of comparative analysis requires prior knowledge of associations between methylation profiles associated with CpG sites (e.g. from different organs) as well as knowledge of specific quantitative values associated with these correlations such that meaning full comparisons can be made. A review of the specification teaches that the system “may establish two or more thresholds for a CpG probe to be selected. The first threshold may be based on a variability metric that quantifies how much the probe’s observed data deviates from its expected behavior, which is determined at stage 420. The second threshold may be related to the model metric that represents the magnitude of change or variability between specific conditions (for example, across different age groups, health conditions, or other effectors). In some cases, this second threshold could be based on the standard deviation or another metric that captures the spread of variability across conditions, which is determined at stage 434. The thresholds define cut-off values for selection” [0125-126]. However, this does not provide sufficient technical details given the full scope of what is claimed. While information which is well known in the art need not be described in detail in the specification, it is not enough that one skilled in the art could write a program to achieve the claimed functions. Moreover, a review of the prior art teaches that such limitations are not trivial. For example, Christensen et al. (PLOS Genetics, 2009, Vol. 5, Issue 8, e1000602, pp.1-13) teaches methods for profiling CpG methylation of normal human tissues for characterizing the role of aging and environmental exposures in interindividual methylation variation using machine learning models. Unlike the claimed invention, Christensen teaches obtaining methylation levels from a plurality of specific CpG locations [page 11, Data Assembly]; analyzing non-pathologic human tissues from 10 different anatomical sites (i.e. organs) at 1,413 autosomal CpG loci associated with 773 genes to discern how aging and exposures contribute to normal variation in methylation [Abstract]. Christensen also determines methylation profiles using unsupervised modeling [Abstract, Figures 1 and 2, Tables 1 and 2]. As discussed above, Jones also teaches that DNA methylation profiles are highly divergent in different tissues, and that comparing DNA methylation across tissues presents many unique challenges [page 925, col. 2]. As such, there is insufficient evidence of possession of information relating to analysis and threshold values for the full scope of what is encompassed by the claims.
For the reasons discussed above, the specification does not provide information to demonstrate to one of ordinary skill in the art that the inventor possessed the invention at the time the application was filed. For more information regarding the written description requirement, see MPEP §2161.01- §2163.07(b).
Claim rejections - 35 USC § 112b
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, 3-9, 13, 14, 15 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. Claims that depend directly or indirectly from claim(s) 1 are also rejected due to said dependency.
Claim 1 recites the term “functional organismal aging”. It is unclear as to the metes and bounds of this term such that the artisan would recognize what limiting effect is intended, i.e. in what way is ‘aging’ different from ‘functional organismal aging’. A review of the specification does not provide any limiting definition of this term that would serve to clarify the scope. The specification does recite “functional organ analysis” throughout [0012, 0046]. However, this is not commensurate in scope with what is being claimed and it is improper to import narrowing limitations into the claims. MPEP 2111.01. Clarification is requested via amendment.
Claim 1 recites “identify….a first subset of the CpG sites by filtering out CpG sites that do not satisfy at least one variability threshold, the first subset…determined to be associated with the first organ based on variability analysis.” It is unclear in what limiting effect is intended by the phrase “based on variability analysis”. Such generic functional claim language amounts to descriptions of problems to be solved and covers all means or methods of performing the claimed function. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. A review of the specification generically discloses models that allow for dynamic grouping and ranking of features using variability analysis and unsupervised clustering [0028]. However, this does not amount to a limiting definition with regards to the intended computational operations and it is improper to import narrowing limitations into the claims. MPEP 2111.01. As a result, it is unclear what computational techniques are included or excluded by the claim language such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment.
Claim 1 recites “generate an organ-specific biological-age profile characterizing functional organismal aging of the first organ based on analyzing the longitudinal variations.” It is unclear in what way generating the claimed biological-age profile is “based on analyzing the longitudinal variations”. Such generic functional claim language amounts to descriptions of problems to be solved and covers all means or methods of performing the claimed function. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. A review of the specification generically discloses organ-specific age profiles generated by an entropy analysis system [Figure 6 and ¶0062-0064]. However, this is not commensurate in scope with what is claimed and it is improper to import narrowing limitations into the claims. MPEP 2111.01. As a result, it is unclear what computational techniques are included or excluded by the claim language such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment.
Claims 3 and 6 recite “applying a model”. It is unclear as to the metes and bounds of the claimed “model” such that the artisan would recognize what internal structures are intended, i.e. what is scope of the claimed model and in what way is it being applied. For example, the artisan would recognize that a model generally requires various parameters that must be defined mathematically before the model can be used. However, the instant claims do not define the model in terms of parameters nor do they set forth any steps involved in the method/process of application. As a result, it is unclear what method/process applicant is intending to encompass to achieve the claimed function. Clarification is requested via amendment. As Applicant has not provided any illuminating arguments or amendments, this rejection is maintained.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PABLO S WHALEY whose telephone number is (571)272-4425. The examiner can normally be reached between 1pm-9pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anita Coope can be reached at 571-270-3614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PABLO S WHALEY/Primary Examiner, Art Unit 3619
