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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/02/2026 has been entered.
This Office Action is in reply to Applicants’ correspondence of 04/02/2026.
Applicants’ remarks and amendments have been fully and carefully considered but are not found to be sufficient to put this application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicants’ amendments. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action.
This Action is NON-FINAL.
Election/Restrictions
In the reply filed on 06/05/2025 Applicants elected, with traverse, the invention of Group 1 (claims directed to predicting age). The requirement was deemed proper and is made FINAL as set forth on page 2 of the Office Action of 07/10/2025.
Additionally, as set forth on pages 2-3 of the Office Action of 07/10/2025, the election as set forth in the reply of 04/24/2025 was extended to the combination of CpG sites provided in Table 1.
Withdrawn Claim Objections
The claim objection set forth on page 3 of the Office Action of 01/09/2026 is withdrawn in light of the amendments to the claims.
New Claim Objections
Necessitated by Amendments
Claim 43 s objected to because of the following informalities: at the end of step (c) there are two semicolons where only one semicolon is required.
Appropriate correction is required.
Withdrawn Claim Rejections - 35 USC § 112 - Indefiniteness
The rejections of claims under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as set forth on page 4 of the Office Action of 01/09/2026, are withdrawn in light of the amendments to the claims.
New Claim Rejections - 35 USC § 112 – Indefiniteness
Necessitated by Amendments
Claims 43-62 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.
Claims 43-62 are unclear over purpose of the claimed methods as “for measuring age”, as recited in the preamble of claim 43, from which claims 44-62 depend. There is no process step in which age is measured. The relevant step of the claims is performed in step (c) which concludes with “establishing an epigenetic age and predicting the chronological age of the subject or population to be tested”, but the ages are not “measured” where the “epigenetic age” is “established” via a “statistical prediction method” and the “chronological age” is predicted but not measured.
Claim 51 and 58 are unclear over recitation of the phrase “selection of the CpG sites that define the clock is performed with penalized regression”, as recited in each of claim 51 and 58, because there is no step of selection for the recited CpG sites. The independent claim requires “determining methylation levels of a set of specific CpG sites” and defines the particular sites of the set, so there is no aspect of the claim that requires their selection.
Claims 59-62 are unclear over recitation of limitations related to the treatment of the Gallus gallus subject or population, for example as recited in claim 59 as:
the Gallus gallus subject or population is administered a health promoting substance
because the claims depend form claim 43 which sets forth that “if such intervention is indicated, feeding or administering a health promoting zootechnical feed additive or therapeutic agent to the Gallus gallus subject or population”. Where the “feeding or administering” appears to be conditional upon some particular use of the established epigenetic age as an indicator, it is unclear if the rejected claims are intended to in fact require that the use of the epigenetic age as an indicator has indicated a need for therapeutic or nutritional intervention.
Claim Rejections - 35 USC § 112 – Failure to Limit
Claim 48 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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.
Claim 48 recites a limitation requiring that “step (b) includes a DNA methylation profiling process”, but step (b) in claim 43 (from which the rejected claim depends, recites “determining methylation levels of a set of specific CpG sites in the genomic DNA”, where “determining methylation levels of a set of specific CpG sites” is itself a process of methylation profiling.
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 Rejections - 35 USC § 101
Claims 43-62 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception to patentability encompassing abstract ideas and a natural phenomenon without significantly more.
The claim(s) recite(s) a steps of normalizing determined methylation levels, and using a statistical prediction method to apply a trained regression function to process normalized levels relative to reference levels. These calculations (normalization; comparisons using a statistical method) fall under the mathematical calculation grouping of abstract ideas (see MPEP 2106.04(a)(2)(I)(C)). The claims additionally recite the using an epigenetic age to indicate the need for therapeutic or nutritional intervention; where such as the evaluation of data or information to reach a conclusion is also an abstract idea (see MPEP 2106.04(a)(2)(III)). Additionally, where the claims are directed to a correlation between methylation status, epigenetic age, chronological age, the need for a treatment, the claims are directed to the natural association between age and methylation, and health and methylation, and thus are directed to a natural phenomenon (see MPEP 2106.04(b) I).
This judicial exception is not integrated into a practical application because there are no required practical steps related to any particular predicted chronological age. Here it is noted that while the claims recite, in step (d) of claim 43, steps related to “feeding or administering a health promoting zootechnical feed additive or therapeutic agent to the Gallus gallus subject or population”, such step are preformed “if such intervention is indicated” by “the established epigenetic age”. As such the ““feeding or administering” is conditional upon a particular indication, but that indication is not require to be present and detected (see MPEP 2106.04(d)(2)). Here it is noted that claim 59-62 appear to recites limitations related to the treatment of the Gallus gallus subject or population, this aspect of the claims has been addressed previously in this Office Action under 35 USC 112 as unclear. Furthermore it is note that the concept of administering some generic health promoting therapeutic agent to a subject that is broadly determined to be in need therapeutic intervention is so general as to merely be and instruction to apply the judicial exception where epigenetic status is treated to health (see MPEP 2106.04(d)(2)).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the data gathering steps of the claims (i.e.: obtaining genomic DNA and determining a methylation level of CpG sites) is activity that was well understood, routine, and conventional in the related art. The specification teaches detection of CpG methylation is performed using commercially available reagents and known techniques (e.g.: pages 14-15). Additionally, the prior art of Zhang et al (2017) (cited on the IDS of 10/26/2022) teaches the analysis of CpG methylation in samples from Gushi hens, including comparisons at different ages, using whole-genome bisulfite sequencing.
Thus the claims are properly rejected as being directed to a judicial exception to patentability without significantly more.
Response to Remarks
Applicants have traversed the rejection of claims under 35 USC 101 as being directed to a judicial exception to patentability without significantly more. Applicants’ arguments (p.7-9 of the Remarks of 04/02/206) have been fully considered but are not persuasive to withdrawn the rejection as maintained above.
Applicants have asserted that the judicial exceptions of the claims are integrated into a practical application because the claim includes a further step of using the established epigenetic age, as an indicator whether therapeutic or nutritional intervention is needed for the subject or population. The Examiner maintains that “using” the epigenetic age “as an indicator” is itself representative of a judicial exception as set forth in the rejection, the step is the evaluation of data or information to reach a conclusion. Furthermore, the claims fail to require the administration of any therapeutic intervention because the claims recite that the feeding or administering is conditional, and performed “if such intervention is indicated”; therefore when intervention is not indicated, there are no additional steps related to therapeutic treatment.
Claim Rejections - 35 USC § 112 – Scope of Enablement
Claims 43-62 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for (consonant with the election) methods wherein:
the epigenetic age of the Gallus gallus subject or population being greater than the chronological age of the Gallus gallus subject or population is an indicator of the need for therapeutic or nutritional intervention.
does not reasonably provide enablement for the methods as claimed which broadly recite steps of “establishing an epigenetic age and predicting the chronological age of the subject or population to be tested”, and “using the established epigenetic age, as an indicator of whether therapeutic or nutritional intervention is needed”.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Nature of the invention and the breadth of the claims
The rejected claims are directed to methods of indicating the need for a therapeutic intervention based on any use of an epigenetic age established in a subject Gallus gallus or population. The claims thus require knowledge of a reliable relationship between any epigenetic age and the need to treatment.
Direction provided by the specification and working example
The instant specification provides an example (p.14) of the analysis of chronological age and methylation status in chickens (Gallus gallus). The specification teaches that methylation from particular tissues was compared among three age-correlated reference populations, and that a set of 45 particular CpGs (relevant to the election) was identified by as indicative of chronological age using statistical analysis of the methylation.
The specification teaches (p.16) that for the analysis of a new sample the methylation ratios of the 45 particular CpGs must be provided.
Relevant to the limitations of the rejected claims, the application as filed specifies that “epigenetic age acceleration (epigenetic age>chronological age) suggests that the underlying tissue ages faster than expected on the basis of chronological age”, and that “epigenetic age acceleration is associated with a great number of age-related conditions and diseases, such as inflammatory processes”. The application further provides that “epigenetic age of a non-inflamed Galliformes subject or of a non-inflamed Galliformes population corresponds to its chronological age”.
State of the art, level of skill in the art, and level of unpredictability
While the state of the art and level of skill in the art with regard to the analysis of methylation levels of CpGs in any sample is high, the unpredictability in associating any methylation levels with a particular chronological age is higher. Such unpredictability is demonstrated by the related art and the instant specification.
Stubbs et al (2017) teaches that age-related methylation is different among different tissues. And Bell et al (2019) teaches several aspects related to the unpredictability of using CpG methylation to establish a chronological age of a subject.
Because the claims generically encompass any use of an epigenetic age, whereas the application as filed teaches only that finding an epigenetic age is older than a chronological age in indicative of age-related conditions and diseases, it is unpredictable as to how any epigenetic age as recited in the claim would be used to indicate a need for intervention.
Quantity of experimentation required
A large and prohibitive amount of experimentation would be required to make and use the claimed invention. Such experimentation would require case:control analysis of samples from any subjects of interest to try to establish the broadly required associations of the claims. Even if such experimentation were to be performed, given the unpredictability of the subject matter of the claims, there is no assurance that the required associations would beyond those specifically disclosed in the application would be detected.
Conclusion
Taking into consideration the factors outlined above, including the nature of the invention and breadth of the claims, the state of the art, the level of skill in the art and its high level of unpredictability, the lack of guidance by the applicant and the particular examples, it is the conclusion that an undue amount of experimentation would be required to make and use the invention in the full scope as claimed.
Response to Remarks
Applicants have traversed the rejection of claims under 35 USC 112 as encompassing subject matter not enabled by the application as originally filed. Applicants’ arguments (p.11 of the Remarks of 04/02/2026) have been fully considered but are not persuasive to withdrawn the rejection as maintained above.
The arguments of the remarks are directed to the rejection as it was applied to the previous claims. The Examiners maintains, as set forth in the instant rejection, that the claims broadly encompass any use of any established epigenetic age, as an indicator of whether therapeutic or nutritional intervention is needed, whereas the application as originally field provide only for the comparison of a calculated epigenetic age with a known chorological of the subject/population is useful for indicating a need for therapeutic intervention.
Withdrawn Claim Rejections - Double Patenting
The rejection of claims for double patenting made over the conflicting claims of a co-pending application, as set forth on pages 16-18 of the Office Action of 01/09/2026, is withdrawn in light of the amendments to the claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
Prosecution Insights