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 .
Applicants Amendment
Applicants amendment filed 12/9/2025 has been received and entered. Claim has been amended, claim 4 has been cancelled and claims 14-15 have been added.
Claims 1-3, 5-15 are pending and currently under review.
Election/Restriction
Applicant's election with traverse of Group I in the reply filed on 5/27/2025 was acknowledged. No new arguments are provided, and the requirement is still deemed proper and FINAL.
Claims 1-3, 5-15 are pending. Claims 8-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 5/27/2025.
Newly added claims 14-15 are dependent on claim 1 and appear consistent with the examined invention.
Claims 1-3, 5-7, 14-15, drawn to a method for establishing a chicken methylation clock are currently under examination.
Priority
This application filed 6/10/2022 is a 371 national stage filing of PCT/EP2020/085085 filed 12/8/2020 and claims benefit to foreign application PCT/EP2019/085021 filed 12/13/2019.
Receipt was acknowledged of certified copies of papers required by 37 CFR 1.55.
See paper entered 6/10/2022.
Response to Applicants comments
Applicants note the previous filings and claim for priority, noting MPEP 1842 for proper claim of priority.
In response, Applicants’ summary is noted, however in the filing of the ADS the claim to foreign application PCT/EP2019/085021 filed 12/13/2019 was made directly to the instant application and not through the previous priority claim of PCT/EP2020/085085 filed 12/8/2020. Because PCT/EP2019/085021 filed 12/13/2019 is more than a year prior to the instant application, the benefit to priority is not proper as it is over a year prior to 6/10/2022 filing date of the instant application.
It appears that a new ADS form with the proper claim of priority and necessary petition requests may remedy the issue.
Acknowledgment is made of applicant's claim for priority under 35 U.S.C. 119(a)-(d) or (f), 365(a) or (b), or 386(a) based upon an application filed in EP on 12/16/2019. The claim for priority cannot be based on said application because the subsequent nonprovisional or international application designating the United States was filed more than twelve months thereafter and no petition under 37 CFR 1.55 or request under PCT Rule 26bis.3 to restore the right of priority has been granted.
Applicant may wish to file a petition under 37 CFR 1.55(c) to restore the right of priority if the subsequent application was filed within two months from the expiration of the twelve-month period and the delay was unintentional. A petition to restore the right of priority must include: (1) the priority claim under 35 U.S.C. 119(a)-(d) or (f), 365(a) or (b), or 386(a) in an application data sheet, identifying the foreign application to which priority is claimed, by specifying the application number, country (or intellectual property authority), day, month, and year of its filing (unless previously submitted); (2) the petition fee set forth in 37 CFR 1.17(m)(3); and (3) a statement that the delay in filing the subsequent application within the twelve-month period was unintentional. The petition to restore the right of priority must be filed in the subsequent application, or in the earliest nonprovisional application claiming benefit under 35 U.S.C. 120, 121, 365(c), or 386(c) to the subsequent application, if such subsequent application is not a nonprovisional application. The Director may require additional information where there is a question whether the delay was unintentional. The petition should be addressed to: Mail Stop Petition, Commissioner for Patents, P.O. Box 1450, Alexandria, Virginia 22313-1450.
Information Disclosure Statement
It was noted that the listing of references in the specification is not a proper information disclosure statement, citing for example page 1, lines 32-35.
No comment nor new IDS has been provided in the instant response.
37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
Claims 1-3, 5-7, stand and newly added claims 14-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 17/759194 (assigned, no action mailed).
Response to Applicants arguments
Applicants note the amendments and argue the rejection is moot, and that the rejection is premature since no allowable subject matter is indicated.
In response, a provisional rejection is made over the claims and is not dependent on allowability of the claims, therefore the general timing of the rejections is proper. With respect to the amendment, both claim sets have steps of obtaining CpG data from age correlated chicken populations and assessing and correlating the methylation patterns that might be observed, and both ending with the indication that the correlation is associated with a chicken methylation clock. When viewed as a whole, the steps of each claim set provides for the same data, same analysis and the same correlation to an age related chicken clock. Applicants do not note any particular step or limitations that distinguishes the two claim sets, and there does not appear to be any specific requirement of the claims that distinguishes one over the other for providing a chicken clock. Therefore, for the reasons above and of record, the rejection is maintained.
The basis of the analysis and a copy of the claim is provided for completeness of the record.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims directed to a chicken are encompassed by the claims of ‘194 encompassing any avian species. The claims in ‘194 directed to avian do not recite a specific species, however review of the specification provides for methylation patterns as methylation clocks and the importance of chickens, Gallus gallus, as an important commercial produce and data obtained from the analysis of chicken. Further, the method recites that the information is obtained by bisulfite sequencing (claim 7), obtained from different tissues (claims 2-5), over the life time (claim 6) and the analysis specifically uses ‘penalized regression’ (claims 1 and 14). Claim 1 of ‘194 has been amended, and is provided for comparison and completeness of the instant record (representing the claim that was analyzed noting the preamble indicates the steps are performed establish an epigenetic clock):
Claim 1. (Currently Amended) A computer-implemented method
[[(a.)]] (a) identifying and determining [[the]] methylation levels of specific CpG sites within [[the]] a genomic DNA obtained from a plurality of different biological sample materials deriving from [[the]] an avian species and representing specific time points within [[the]] a chronological lifespan of [[this]] the avian species,
[[(b.)]](b) excluding all CpG sites associated with single nucleotide polymorphisms from the CpG sites identified in step (a.)(a)
[[(c.)]] (c) excluding all CpG sites located on [[the]] sex chromosomes from the CpG sites obtained in step (b.)Lb),
[[(d.)]] (d,) performing a tissue-specific normalization [[step]] for the CpG sites obtained in step (c.) , and
[[(e.)]] (e) correlating [[the]] CpG methylation levels of the CpG sites obtained in step (d.){d) with chronological age [[using]] with a penalized regression model.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
As noted previously, a timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, newly added claims refer to tables in the specification, and as described in MPEP2173.05(s), claims should be complete in themselves such that incorporation by reference to a specific figure, table, list, etc. from the specification is permitted only in exceptional circumstances. Here, the tables fail to provide a specific ‘site’ and rather point to specific ‘position of C’, and only provide for Gallus gallus which is inconsistent with the breadth of any chicken, and possible variations for the various chromosomes listed.
Providing the specific sites in the claims and consistency of what the data represents would address the basis of the rejection.
Claims 1-3, 5-7, 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, newly amended claim 1 adds that the genome analyzed is ‘located in low methylation regions’ however what these regions are or how ‘low’ is defined is not provided in the claim nor defined in the specification. Further, step c) now requires a ratios using a cutoff value ‘of at least 3’ but the ratio is not provided and it is unclear and undefined what is being calculated and what 3 is to represent. Dependent claims are included in the basis of the rejection because they do not resolve the issue and are required to practice the claim steps.
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 1-3, 5-7, stand and newly added claims 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.
Claim analysis
Claim 1 has been amended and still is generally directed to method of establishing or creating a chicken methylation clock. Specifically, step a) ahs been amended to indicate the source of the genomic DNA is pooled from age correlated chickens and from the same tissue, using low methylation sites which show a ratio of 3, then using regression to provide an equation representing a chicken methylation clock. In view of the specification teachings, encompassed by the claims the data represented by a training set is provided and represented in the data it contains methylation ratio, encompassing whole sample and specific sequences, for samples from different ages of chickens, identifying sites in the data that are informative and that are correlated with changes in age of the chicken using penalized regression of the ratios, and using these as a model for chicken methylation clock.
Dependent claims are not amended and provide for known methods that were used to obtain the data, like bisulfite sequencing (claim 2), providing a list of specific tissues represented in the data (claim 3), and further instructions on optimizing using regression and calculating values in the assessment of the data (claims 4-7). Newly added claims 14 and 15 refer to tables in the specification for various positions of C in the genome.
Response to arguments
Applicants provide a summary of the rejection and note the claims provide for a pooled training sample set, and argue that the combination under prong 2 is patent eligible.
In response, a reasonable interpretation is that the data set is data. Further, the combination is not specifically defined and appears to encompass data. While it could encompass a physical sample, the claims for 101 purposes does not appear to be a practical application as argued. In review of the record, there does not appear to be any additional evidence or consideration as the claim as a whole. Given the record as a whole, the claims appear to be patent eligible. The basis of the analysis is provided below for completeness of he record.
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a process.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of accessing methylation data for possible informative sequences based on methylation patterns present in the data for different aged sources of chickens. The step of aligning and comparing methylated sequences to arrive at the identification of sequences that change with age and which can be used singly or together as a correlative observation are instructional steps. The claim requires simple observations of methylation ratios in different age samples, and identifying those that correlate or demonstrate a consistent change over time and which inform and represent the age of the chicken, also termed a chicken methylation clock in the preamble and final thereby step describing what performing regression analysis does. The judicial exception is a set of instructions for analysis of methylation data and appears to fall into the category of Mathematical Concepts, that is mathematical relationships as required in quantitating ratios, and into the category of Mental Processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion) where here observations and simple ratio calculations can be performed in ones mind with the aid of paper and pen. The breadth of “determining”, “defining”, and performing “regression” encompasses non-transformative visual assessment of data. Here the data is ratios, or sequence information of methylation present in a sequence which can be quantitated into a ratio, and correlating the sites which change of the chronological age of the sample source taken from a chicken using regression. This breadth does not impose a meaningful limit on the claim scope beyond observing and analyzing the data to provide a correlation associated between age and methylation changes. Although the claims recite obtaining a chicken methylation clock, this appears to be just data representing the identified correlation and the courts have also identified limitations that did not integrate a judicial exception into a practical application; for example, merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f). The recited breeding crosses are interpreted as naturally occurring plant crosses. As the steps of the claims together reasonably are interpreted as mere data gathering and analysis. Computing, constructing datasets and using statistical models was well understood, conventional, and routinely performed in the art at the time the application was filed. See also MPEP § 2106.05(h) for a discussion on generally linking the use of a judicial exception to a particular technological environment or field of use. The claims appear to fall into the category of Mathematical Concepts, as it applies the use of statistics and mathematical relationships in analyzing probabilities, and also into the category of mental processes, as concepts performed in the human mind (including an observation, evaluation, judgment, opinion) because there is no apparent complexity to or amount of data that is collected and analyzed as presently claimed.
Recent guidance from the office requires that the judicial exception be evaluated under a second prong to determine whether the judicial exception is practically applied. In the instant case, the claims do not have an additional element recited in the claims. This judicial exception requires steps recited at high level of generality and to the extent that analysis of data can be practiced using a computer the instructions of required of the analysis appear to be only stored on a non-transitory medium, performed using a processor, or using a general purpose computer, and is not found to be a practical application of the judicial exception as broadly set forth.
For step 2B of the 101 analysis, each of the independent claims recites additional elements and are found to be the steps of obtaining methylation data represented in a training set. As such, the claims do not provide for any additional element to consider under step 2B. To the extent that such data can be analyzed more quickly using a computer, it is noted that in explaining the Alice framework, the Court wrote that "[i]n cases involving software innovations, [the step one] inquiry often turns on whether the claims focus on the specific asserted improvement in computer capabilities or, instead, on a process that qualifies as an abstract idea for which computers are invoked merely as a tool." The Court further noted that "[s]ince Alice, we have found software inventions to be patent-eligible where they have made non-abstract improvements to existing technological processes and computer technology." Moreover, these improvements must be specific -- "[a]n improved result, without more stated in the claim, is not enough to confer eligibility to an otherwise abstract idea . . . [t]o be patent-eligible, the claims must recite a specific means or method that solves a problem in an existing technological process." As indicated in the summary of the judicial exception above and in view of the teachings of the specification, the steps are drawn to analysis of methylation data. While the instructions can be stored on a medium and could be implemented on a computer, together the steps do not appear to result in significantly more than a means to compare sequences. The judicial exception of the method as claimed can be performed by hand and in light of the previous claims to a computer medium and in light of the teaching of the specification on a computer. In review of the instant specification the methods do not appear to require a special type of processor and can be performed on a general purpose computer. Dependent claims set forth additional steps which are more specifically define the considerations and steps of calculating, and comparing, and do not add additional elements which result in significantly more to the claimed method for the analysis. Additionally, Step 2B of the two step analysis is to determine whether any element or combination of elements, in the claim is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception. In review of the art, for the acknowledgement of the necessary methylation data and possible physical means of obtaining it, the teachings of Li et al. are noted for providing evidence that such limitations were known and conventional as demonstrated in the genome-wide promoter DNA methylation analysis in chickens. More specifically, what is observed is epigenetic modification patterns allow the analysis of context dependent information on DNA. “DNA methylation represents the best-understood epigenetic modification and is characterized by high specificity for CpG dinucleotides in animal genomes.” No additional steps are recited in the instantly claimed invention that would amount to significantly more than the judicial exception than the analysis of the data. Without additional limitations, a process that employs mathematical algorithms (analyzing sequences for methylation patterns) to manipulate existing information to generate additional information (a chicken methylation clock) is not patent eligible. Furthermore, if a claim is directed essentially to a method of calculating, using a mathematical formula, even if the solution is for a specific purpose, the claimed method is non-statutory. In other words, patenting abstract idea (designing probes to a target sequence) cannot be circumvented by attempting to limit the use to a particular technological environment or purpose and desired result.
One way to overcome a rejection for non-patent-eligible subject matter is to persuasively argue that the claimed subject matter is not directed to a judicial exception. Another way for the applicants to overcome the rejection is to persuasively argue that the claims contain elements in addition to the judicial exception that either individually or as an ordered combination are not well understood, routine, or conventional. Another way for the applicants to overcome the rejection is to persuasively argue that the claims as a whole result in an improvement to a technology. Persuasive evidence for an improvement to a technology could be a comparison of results of the claimed subject matter with results of the prior art, or arguments based on scientific reasoning that the claimed subject matter inherently results an improvement over the prior art. The applicants should show why the claims require the improvement in all embodiments.
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.
Claims 1-3, 5-7 rejected under 35 U.S.C. 103 as being unpatentable over Gryzinska et al. (2013, of record), Horvath et al. (2018, of record), Li et al. (of record), Naue et al. (2018, of record) and Bocklandt et al. (2011, of record) is withdrawn.
In view of the amendments, the cited references fail to provide for all the limitations of the amended claims.
Conclusion
No claim is 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.
In review of the art, method of obtaining methylation information about a genome and changes in methylation were well known. For example, Gryzinska et al. teach that methylation plays an important role in the normal development of organisms, and methylation patterns can be correlated with age. Gryzinska et al. demonstrate that DNA methylation in chickens change with age after the post-embryonic stage. More generally, Horvath et al. demonstrate changes in DNA methylation-based biomarkers and the epigenetic clock theory of ageing. More generally, Horvath et al provide an overview that a particularly prominent example for an epigenetic biomarker is provided by DNA methylation clocks, which are sets of CpG specific methylation values that, in combination with a mathematical algorithm, estimate the age of the DNA source. While the methylation level of individual CpGs can exhibit a relatively weak correlation with age, methylation clocks are composite multivariate biomarkers that have been shown to accurately measure age in humans and mice. In addition to the data provided in Gryzinska et al., the teaching of Li et al. provide evidence for obtaining genome-wide data to demonstrate mapping of promoter DNA methylation in chickens and in a variety of tissue types. What is observed is that epigenetic modification patterns allow the analysis of context dependent information on DNA. DNA methylation represents the best-understood epigenetic modification and is characterized by high specificity for CpG dinucleotides in the genome. Additionally, the teachings of Naue et al. provide analysis of human blood samples from different age subjects and demonstrate that informative methylation patterns can be identified and can be used to correlate to chronological age, as well as Bocklandt et al. demonstrate that epigenetic changes in methylation can be used as a predictor of age, and provide analysis of global and gene specific methylation patterns to demonstrate that novel loci can be correlated with age.
However, the art of record fails to provide any motivation to create a LMR CpG chicken methylation clock as required of the claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Joseph T Woitach whose telephone number is (571)272-0739. The examiner can normally be reached Mon-Fri; 8:00-4:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz R Skowronek can be reached at 571 272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Joseph Woitach/Primary Examiner, Art Unit 1687
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