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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on May 6, 2026 is acknowledged. The traversal is on the ground(s) that claims of the present application would be part of an overlapping search area, relevant subclasses without substantial additional effort and that the election of the species chr8:25907849-25907950 and chr8:25907698-25907894 of claim 22 are both encompassed within the range of chr8:25699246-25907950 detected in claim 3 and that both the first and second groups involve the detection of a disease through the detection of EBF2 markers, sharing a common technical feature and thus possessing unity. This is not found persuasive because the arguments directed to “search” and examination burden does not apply for determining a unity of invention. As discussed below, the special technical feature of determining the modification status of EBF and association to pancreatic cancer/tumor is deemed to lack novelty and/or is obvious. For these reasons, the unity of invention is lacking and the restriction is maintained.
The requirement is still deemed proper and is therefore made FINAL.
Claims 22, 24-27, 55, and 56 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on May 6, 2026.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55 for foreign applications ending ‘924.0; ‘281.8; ‘903.9; ‘099.6; ‘984.3; ‘980.5; ‘040.8; ‘055.4; ‘038.0; and 957.6.
Acknowledgment is made of applicant's claim for foreign priority based on two applications filed in China on December 24, 2021 (i.e., the ‘328.8 and the ‘215.8 application). It is noted, however, that applicant has not filed a certified copy of these applications as required by 37 CFR 1.55.
Information Disclosure Statement
The IDS received on December 18, 2023; May 13, 2025; August 19, 2025; and June 26, 2026 are acceptable.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because some of the texts of the figures are poor in quality and are illegible. For example, Figure 1 contains third box of a flow-diagram whose texts are too small and poor in quality to be legible; Figures 4, 5, 21, 22, 24, and 37-39 contain x-axis text which are also illegible . Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
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 3 and 17 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 3 is indefinite for the following reasons. Claim 3 depends from claim 1.
Claim 1 is limited to the determination of a modification status of a DNA region with gene EBF or a fragment thereof. Claim 3 however recites that this DNA region includes a chromosomal region that is greater than that which contains the EBF gene. Therefore, it becomes unclear whether the method is actually assaying the DNA region whose status is being determined is limited to EBF or its fragment or regions not necessarily limited to EBF or its fragment.
The former interpretation is assumed for the purpose of prosecution.
Claim 17 is indefinite because the claim is circular in format. Claim 17 recites that the determining the presence and/or content of the modification status comprises determining the presence and/or content of a DNA region with the modification status or a fragment thereof. The “DNA region with modification status or a fragment thereof” has already been required in parent claim 1 and therefore, claim 17 apparently adds no additional limitation.
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, 4, 6, 8, 10, 12, 14, and 16-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The rejection is applied in two parts. The first part is based on the claims reciting abstract idea, that embraces data harvesting and crunching as well as mental determination. The second part is based on he claims reciting a natural correlation that exists between the modification status of DNA in EBF2 gene or its fragment to pancreatic tumor risk. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons discussed below based on the analysis under the current Patent Eligibility Guidelines (herein, “PEG”) as discussed below.
Step 1 Inquiry under PEG
Step 1 inquiry under Patent Eligibility Guidelines (herein, “PEG”) determines whether or not the claimed invention is drawn to one of the recognized statutory classes of invention. Claim 1 and its dependents (claims 3, 4, 6, 8, 10, 12, 14, and 16-20) satisfy the present inquiry as being drawn to a method.
Step 2A Inquiry under PEG
A recently revised PEG now performs step 2A inquiry under a 2-prong analysis, and the subject claims analyzed accordingly as follows:
Prong 1:
Prong-1 inquiry under step 2A determines whether the claims recite an abstract idea, a law of nature, or a natural phenomenon. As stated above, the breadth of claim 1 embraces two different embodiments both of which read of judicial exception, one in the form of abstract idea (i.e., mental steps and data harvesting/manipulation), and the other in the form of a natural correlation which exists between a subject’s predisposition to pancreatic tumor/cancer and the modified status of a DNA region harboring EBF2 and/or its fragment.
I – Mental steps/Data harvesting and/or manipulation:
Claim 1 recites a step of “determining” a presence and/or content of a modification status of a DNA region with gene EBF2 or a fragment thereof, which could be simply looking at a sequence report and making a mental note, which is considered purely abstract without any application of this judicial exception in a significant way. While the phrase, “in a sample to be tested” is additionally recited in the claim, the phrase could be simply pointing to the source form which the sequence report had been generated and therefore, does not amount to any significant contribution to the mental step.
II – Naturally existing correlation:
Claim 1 also embraces an embodiment of determining the risk that exist between the modification status of a DNA region with gene EBF2 or a fragment thereof and pancreatic cancer. This is a natural correlation that is recited without additional elements to apply it in a significant manner.
Therefore, both embodiments embraced by the claims recite and embrace a judicial exception.
Prong 2:
Prong-2 inquiry under step 2A determines whether or not the claims recite additional elements that integrate the judicial exception into a practical application in a manner that imposes a meaningful limit on the judicial exception.
I – Mental Steps:
The Office notes that some of the dependent claims under this interpretation satisfies the patent eligibility requirement and therefore, only the explicitly discussed claims should be considered rejected.
Claim 3 recites that the DNA region is “derived from human chr8:25699246-25907950.” However, this only further clarify the location from which the sequence information is generated and does not add to the data which is being mentally interpreted. Therefore, the claim does not significantly add more to the judicial exception.
Claim 4 fails to meaningfully limit the judicial exception because the step of obtaining a nucleic acid in the sample to be tested is deemed insignificant extra-solution activity as discussed in MPEP 2106.05(g):
“[p]erforming clinical tests on individuals to obtain input for an equation”
Claim 6 similarly recites the additional limitation that the sample “to be tested includes tissue, cells and/or body fluids.” However, as stated immediately above, this only further describes the source of the sample from which the data was generated and therefore lacks a meaningful application of the judicial exception.
Claim 8 recites the limitation, “further comprising converting the DNA region or fragment thereof” without further clarifying what the conversion is. Therefore, based on BRI, this limitation could read digital conversion of the sequence being read and therefore, reads on data harvesting that is interpreted, failing to add significantly more than the judicial exception.
Claims 10, 12, and 16-19, similarly embrace data harvesting, that is, converting the signal produced into a data (sequence report) that is interpreted and means by which the data had been produced, not necessarily performing the recited step such as PCR.
II – Naturally existing correlation (applies to all claims):
Claim 1 does not recite any additional feature than the generic means of determining the modification status of DNA and its correlation tied to the predisposition of a subject to pancreatic cancer and therefore fail to add any additional elements to this judicial exception.
Claim 3 further recites the location of the region (in the form of chromosomal location) whose modification status is naturally correlated to pancreatic cancer disposition, but the location of the region is also a natural correlation tied to the judicial exception and therefore fails to add significantly more.
Claim 4 recites an additional step of obtaining a nucleic acid in the sample. However, this is considered an “insignificant extra-solution activity” to the judicial exception, generically recited and means to apply the judicial exception (see MPEP 2106.05(g)1).
Claims 6, 10, 12, 14, and 16-20 similarly recite additional elements in form of steps that are implemented to determine the base modification status of the DNA region that is tied to the judicial exception. However, the additional elements are deemed insignificant because they are recited in generic fashion2, failing to impose a meaningful limit on the claims.
As explained by the Supreme Court, in order to transform a judicial exception into a patent-eligible application, the additional element or combination of elements must do ‘more than simply stat[e] the [judicial exception] while adding the words ‘apply it’”. Alice Corp. v. CLS Bank, 573 U.S. __, 134 S. Ct. 2347, 2357, 110 USPQ2d 1976, 1982-83 (2014) (quoting Mayo Collaborative Servs. V. Prometheus Labs., Inc., 566 U.S. 66, 72, 101 USPQ2d 1961, 1965). Thus, for example, claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 134 S. Ct. at 2358, 110 USPQ2d at 1983. See also 134 S. Ct. at 2389, 110 USPQ2d at 1984 (warning against a § 101 analysis that turns on “the draftsman’s art”) (MPEP 2106.05(f))
Step 2B Inquiry under PEG
Step 2B inquiry of the PEG determines whether or not additional elements are provided and whether such elements amount to significantly more than the judicial exception in the claims.
I – Mental Steps:
Claim 3 recites that the DNA region is “derived from human chr8:25699246-25907950.” However, this only further clarify the location from which the sequence information is generated and does not add to the data which is being mentally interpreted. Therefore, the claim does not significantly add more to the judicial exception.
Claim 4 fails to meaningfully limit the judicial exception because the step of obtaining a nucleic acid in the sample to be tested is deemed insignificant extra-solution activity as discussed in MPEP 2106.05(g):
“[p]erforming clinical tests on individuals to obtain input for an equation”
Claim 6 similarly recites the additional limitation that the sample “to be tested includes tissue, cells and/or body fluids.” However, as stated immediately above, this only further describes the source of the sample from which the data was generated and therefore lacks a meaningful application of the judicial exception.
Claim 8 recites the limitation, “further comprising converting the DNA region or fragment thereof” without further clarifying what the conversion is. Therefore, based on BRI, this limitation could read digital conversion of the sequence being read and therefore, reads on data harvesting that is interpreted, failing to add significantly more than the judicial exception.
Claims 10, 12, and 16-19, similarly embrace data harvesting, that is, converting the signal produced into a data (sequence report) that is interpreted and means by which the data had been produced, not necessarily performing the recited step such as PCR.
II – Naturally existing correlation (all claims):
Claim 1 does not recite any additional feature than the generic means of determining the modification status of DNA and its correlation tied to the predisposition of a subject to pancreatic cancer and therefore fail to add any additional elements to this judicial exception.
Claim 3 further recites the location of the region (in the form of chromosomal location) whose modification status is naturally correlated to pancreatic cancer disposition, but the location of the region is also a natural correlation tied to the judicial exception and therefore fails to add significantly more.
Claim 4 recites an additional step of obtaining a nucleic acid in the sample. However, this is considered an “insignificant extra-solution activity” to the judicial exception, generically recited and means to apply the judicial exception (see MPEP 2106.05(g)3).
Claims 6, 10, 12, 14, and 16-20 similarly recite additional elements in form of steps that are implemented to determine the base modification status of the DNA region that is tied to the judicial exception. For example, in order for the DNA modification status to be determined, a sample of interest must be collected, the sequence treated and processed to determine the base modification (i.e., methylation status). These steps are, however, recited in a generic fashion as well as involving routine and conventional means (i.e., methylation-sensitive restriction assay, or bi-sulfite treatment of the sample, and qPCR means of detection). When such extra-solution limitation is well known, routine and conventional in the art, such limitations fail to add additional elements and fail to impose a meaningful limit on the claims. Therefore, the present claims lack patent eligibility.
Claim Rejections - 35 USC § 102
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, 3, 4, 6, 8, 10, 12, 14, and 16-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hong et al. (Human Cancer Biology, 2012, vol. 18, no. 3, pages 700-712; IDS ref).
With regard to claim 1, Hong et al. teach a method of determining a risk of developing pancreatic tumor (“[o]ur goal was to conduct genome-wide CpG island methylation profiling to identify aberrantly methylated loci in IPMNs4”), comprising the step of determining a presence and/or content of a modification status of DNA region with gene EBF2 or a fragment thereof in a sample to be tested (“we find that the pancreatic precursor neoplasms known as IPMNs are characterized by widespread aberrant hypermethylation affecting several hundred CpG islands … we find that even low-grade IPMNs harbor aberrant methylation of hundreds of CpG islands, with evidence of increased levels of methylation with increasing neoplastic grade …”, see page 709, 2nd column, Discussion; also “there were 10,323 uniquely hypermethylated probes in at least 1 of the 6 IPMN/normal pancreatic duct pairs representing 2,195 loci and 2,244 genes (Supplementary Table S3)”, page 703, 2nd column), wherein Table S3 discloses that EBF2 gene was assayed and determined that it was hypermethylated (see gene number 545 in supplemental table 3).
With regard to claim 3, because EBF2 gene was assayed for methylation status, the DNA region is necessarily met.
With regard to claims 4 and 6, sample is obtained for analysis (“[g]enomic DNA was extracted from the microdissected samples …”, page 702, 1st column).
With regard to claim 8, 10, 12, 14, 16, and 17, the sample is treated with bisulfite5 (“[m]icrodissected DNA was treated by sodium bisulfite …”, page 702, 2nd column).
With regard to claim 18, real-time PCR is performed (see page 703, 1st column).
With regard to claim 19, the modification status is discovered via comparison to normal pancreatic duct samples (page 704, 1st column, 1st paragraph).
With regard to claim 20, MCA is performed that amplify the isolated genomic DNA prior to their analysis on the Agilent 244K human promoter and CpG island microarrays (see page 702, 1st column, bottom paragraph and 2nd column, 2nd paragraph).
Because the claims employ the transitional phrase, “comprising”, the method allows the inclusion of additional gene analysis in the method. As Hong et al. teach that the DNA modification status of EBF2 gene is analyzed, along with other genes in their ties to pancreatic cancer disposition, Hong et al. properly anticipate the invention as claimed.
Therefore, the invention as claimed is anticipated by Hong et al.
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YOUNG J KIM/Primary Examiner
Art Unit 1637 July 8, 2026
/YJK/
1 “the addition of extra-solution activity does not amount to an inventive concept” Parker v. Flook, 437 U.S. 584, 588-89, 198 USPQ 193, 196 (1978)
2 “additional element of measuring metabolites of a drug administered to a patient was insignificant extra-solution activity.
3 “the addition of extra-solution activity does not amount to an inventive concept” Parker v. Flook, 437 U.S. 584, 588-89, 198 USPQ 193, 196 (1978)
4 IPMNs are precursors to infiltrating pancreatic ductal adenocarcinomas, see Abstract
5 Treatment with bisulfite converts non-methylated cytosine (deaminates) to uracil while not converting methylated cytosines, thus allowing for the modification status of DNA via a conversion process.
Prosecution Insights