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 .
Election/Restrictions
Applicant’s election without traverse of cg10272901 in the reply filed on 12/22/2025 is acknowledged.
Claims 7-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/22/2025. It is noted that applicant elected the single CpG site, cg10272901. Claims 7-21 read on a combination of CpG sites and a combination of CpG was not elected (see restriction requirement, pg. 4 mailed 09/17/2025).
Claims 1-6 are under examination with respect to cg10272901.
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 1-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more.
Claims 1 recites an abstract idea that is a mental process. Claim 1 recites determining the total methylation level of the one or more CpG sites using the total number. The step of determining total methylation using the total number of CpG site is mental processes. Claim 6 recites if the total DNA methylation level is higher or lower than the corresponding total level in a standard control which is a mental process. Neither the specification or the claims set forth limiting definition for determining or how the total DNA methylation level is determined to be higher or lower than the corresponding total level in a standard control. The claims do not set forth how each of these steps are accomplished and the broadest reasonable interpretation is a step that can be accomplished mentally be evaluating data and critical thinking process such that one mentally reads information from a report regarding the assay results of CpG methylation (claim 1) and mentally compares the results of a methylation assay to a control level (claim 6) then draws a mental conclusion. Such determining and comparison encompass process that may be performed mentally and this is an abstract idea.
This judicial exception is not integrated into a practical application because the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application. For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
Claims 2-5 limit the subject, sample or assay and do not integrate the judicial exception. It is acknowledged that claim 6 does recite comprising administering a specific therapy however this claim is condition. These additional steps/elements are not considered to integrate the judicial exception into a practical application because they merely add insignificant extra-solution activity (data gathering) to the judicial exception and further limit the judicial exception. The administering only occurs if the total DNA methylation level is higher or lower than the corresponding total level in a standard control. A conditional step does not integrate the judicial exception.
As mentioned above, a claim limitation can integrate a judicial exception by applying or using the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. When evaluating this consideration one must the following:
(i) the particularity or generality of the treatment or prophylaxis limitation;
(ii) whether the limitations have more than a nominal or insignificant relationship to the exception; and
(iii) whether the limitations are merely extra solution activity or field of use.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than well-understood, routine, and conventional activities in the art and do not add something significantly more so as to render the claims patent -eligible. The step of performing an assay by contacting DNA with reagents hybridizing to cg10272901 merely instructs a scientist to use well-established routine and conventional nucleic acid techniques to gather samples for diagnostic analysis. As address in the instant specification methods of methylation analysis use commercially available beadchip, Illumina HumanMethylation 450K beadchip (See DNA methylation data, pg. 22).
The step of detecting total methylation level of cg10272901 in a sample constitutes a data gathering step required to apply the law of nature/natural phenomenon. It is acknowledged that the claims name particular CpG sites whose level is to be determined however the claims do not require a particular, non-conventional primer or probe consisting of or comprising a specific nucleotide sequence or any other specific reagent that is used to accomplish such determining such that the claims would recite significantly more than the judicial exception. The targets to be detected are part of the judicial exception and thereby the naming of the targets does not add something “significantly more” to the recited judicial exceptions.
The additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide inventive concept necessary to render the claims patient eligible. There is no combination of elements in this step that distinguishes it from well-understood, routine and conventional data gathering activity engaged in by scientists prior to applicant’s invention and at the time the application was filed. Many cited prior art references in this record demonstrate that these techniques were conventional at the time of the invention. The CpG site, cg10272901 is located on commercially available microarrays, Illumina Human Methylation array, 450K and MethylationEPIC beadchip to determine methylation levels. The prior art of Agardh (BMC Medicine, 2015, 13:182, pp. 1-9), Chambers (2016) and Garcia-Calzon (Sci Transl Med, 12, 2020, pp 1-13) teach using 450 beadchip by Illumina to determine methylation in type I diabetes. Thus the prior art and specification demonstrates it was routine, well-known and conventional in the art to determine methylation levels of cg10272901 in biological samples. The dependent claims do not provide significantly more to the claims outside of the judicial exception as they encompass conventional techniques as described in the instant specification as noted above.
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 1-6 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.
Claim 1 recites the limitation "the total methylation level" in step (d) of the claim. There is insufficient antecedent basis for this limitation in the claim. The preceding steps of the claim recite detecting a total number of the one or more CpG sites based on the signals obtained from the assay. None of the preceding steps require detecting a methylation level at cg10272901, however the final step requires determining the total methylation level of cg10272901 using the total number of CpG sites. Detecting a total number of CpG sites does not necessarily determine or detect a total methylation level at a specific CpG site, as elected. It is unclear if the claim requires determining a total number of CpG sites present or if the claim requires determining the methylation level of the elected CpG cite, cg10272901. Additionally it is unclear what is encompassed by detecting a total number of CpG sites based on the signals. It is unclear what is encompassed and required for “based on”. It is unclear how, when or what is encompassed by detecting total CpG sites based on the signal. Does this encompass the signal detection or some other unstated characteristic of the signal that detects CpG sites? Because it is unclear if the claim requires detecting a total number of CpG sites or detecting the methylation level of cg10272901 and how methylation level is determined based on signals, the claim is indefinite. One of ordinary skill in the art would not be apprised of infringing on the claimed method because the metes and bounds of detecting is unclear.
Claims 2-6 depend from claim 1 and are indefinite for the reasons applied to claim 1.
Claim 6 recites if the total DNA methylation level is higher or lower than the corresponding total level in a standard control, the method further comprising administering to the subject agents for reducing blood glucose and urine protein. The recitation of the corresponding total level in a standard control and administering to the subject renders the claim indefinite. The recitation of “the corresponding total level in a standard control” lacks antecedent basis. None of the previous claims require determining a corresponding total level in a standard control. Is the total level the total level of CpG sites or total level of methylation levels? Additionally it is unclear how both a higher and lower level of methylation at cg10272901 would indicate the same treatment. The specification does not provide a standard for ascertaining the methylation level of cg10272901 or total level of CpG sites with therapy and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chambers, (Lancet Diabetes Endocrinol. 2016, pp 1-21).
Chambers teaches determining genome wide association of DNA methylation in Asians with type 2 diabetes (see patients) (claim 2 and 5). Chambers teaches analysis of DNA methylation levels and total CpG site methylation by using Infinium 450K assay (see pg. 5) (claim 3). Chambers teaches obtaining genomic DNA from peripheral blood samples (see pg. 4) (claim 4). Because Chambers teaches obtaining DNA from blood samples and analysis of DNA methylation by using 450K beadarray, which comprises CpG site cg10272901, Chambers teaches extracting DNA from a blood sample, performing an assay by contacting DNA reagents to CpG site, cg10272901 using 450K beadarray and includes analysis by differential methylation hybridization (reagents include buffers, array). Because Chambers does not teach an increase or decrease of total methylation level at cg10272901 or overall total CpG sites, Chambers meets the limitations of claim 6 because administering only occurs when total DNA methylation is higher or lower than corresponding total level.
Claims 1-4 and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Garcia-Calzon (Sci Transl Med, 12, 2020, pp 1-13).
Garcia-Calzon teaches using 850K array to analyze DNA methylation in blood of patients with type II diabetes treated with metformin (see pg. 1, last paragraph). Garcia-Calzon teaches obtaining genomic DNA from blood samples (claim 4) and teaches performing epigenome-wide association study using Illumina MethylationEPIC array, which comprises probes for cg10272901 (see fig 1) (claim 2 and 3) Garcia-Calzon teaches administering metformin to subjects (claim 6). Because Garcia-Calzon teaches obtaining DNA from blood samples and analysis of DNA methylation by using MethylationEPIC array, which comprises CpG site cg10272901, Garcia-Calzon teaches extracting DNA from a blood sample, performing an assay by contacting DNA reagents to CpG site, cg10272901 using MethylationEPIC array and includes analysis by differential methylation hybridization (reagents include buffers, array).
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SARAE L BAUSCH/ Primary Examiner, Art Unit 1699