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 .
DETAILED ACTION
1. The Applicant’s response to the office action filed on November 06, 2025 is acknowledged.
Status of the Application
2. Claims 1, 5-10, 22 and 29 are pending under examination. New claims 41-45 are added. Claims 30-32 were withdrawn from further considerations as being drawn to nonelected group. The Applicant’s arguments have been fully considered and found persuasive in-part for the following reasons. While incorporating the limitations from the cancelled claims, the amendment recites new limitations that were not present in the previously examined claims. The action is made Final necessitated by the amendment.
The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
Original claims are 1-36 as filed on 10/15/2021.
Misnumbered claims 41-45 have been renumbered as claims 37-41.
Objection to informalities-maintained
3. The disclosure is objected for the following informalities.
(i) claims 2-4 and 22 recite the term ‘cg20655070’. Expanding the abbreviated term at least for the first time that they appear in the claims is suggested. Appropriate correction is required.
Response to Arguments:
With reference to the objection to the informalities, the Applicant’s arguments and the amendment have been fully considered and found persuasive in-part. were fully considered. The amendment to the claims did not address the gene cg20655070 and the objection has been maintained and restated to address the amendment.
Claim Rejections - 35 USC § 112-Withdrawn
4. The rejection of claims under 35 USC 112(b) has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 102-Withdrawn
5. The rejection of claims under 35 USC 102(a)(1) as being anticipated by Mori et al. has been withdrawn in view of the amendment.
6. The rejection of claims under 35 USC 102(a)(1) as being anticipated by Huang et al. has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 103-Withdrawn
7. The rejection of claims under 35 USC 103 as being unpatentable over Huang et al.in view of LIeras et al. has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 101-maintained
8. 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 claimed invention, claims 1, 5-10, 22, 29 and renumbered claims 37-41 are directed to judicial exception without significantly more. The claims 1, 5-10, 22, 29 and 37-41 recite a method of identifying a subject having esophageal squamous cell carcinoma (ESCC) or diagnosing a subject as having a cancer, a process, a statutory category. Claims 1, 5-10, 22, 29 and 37-41 recite a judicial exception (law of nature or natural phenomenon) without significantly more because claims 1, 5-10, 22, 29 and 37-41 recite correlation of the methylation of one or more genes in a subject with ESCC, or correlating methylation of two or more gene markers in a subject with cancer is considered as a law of nature or natural phenomenon, said natural phenomenon exists in nature. This judicial exception is not integrated into a practical application because the judicial exception is not markedly different from the natural phenomenon The claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception because the additional steps (extracting genomic DNA, deamination of DNA, polymerase amplification) do not add significantly more to the claimed method. The additional steps are not themselves natural laws, but neither are they sufficient to transform the nature of the claims because they consist of well-understood, routine, conventional activity already engaged in by the scientific community. The additional steps consist of well-understood, routine, conventional activity already engaged in by the scientific community (Mori et al. (US 2008/0081333); Huang et al. (Int. J. Environ. Res. Public Health, Vol.14, 216, p. 1-12, (2017); Weilin et al. (Clinical Epigenetics, Vo. 9:129, page 1-12, (2017); Lleras et al. (The American Journal of Pathology, Vol. 178(5), p. 1965-1974, (2011)) and Lisa et al. (Cancer Prev Res., Vol. 1(5), page 357-367, (2008)). The additional steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately. The Court has made clear that to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply state the law of nature while adding the words "apply it." Essentially, appending conventional steps specified at a high level of generality, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, phenomena, and ideas patent-eligible. The Courts decision rested upon an examination of the particular claims in light of the Court's precedents, specifically Bilski, Flook and Diehr. The Court repeated the longstanding exceptions (laws of nature, natural phenomena, and abstract ideas) to categories of patent eligibility defined in 35 USC. § 101. In conducting the analysis, the Court addressed the "machine-or-transformation" test explained in Bilski with a reminder that the test is an "important and useful clue" to patentability but that it does not trump the "law of nature" exclusion. A claim that recites a law of nature or natural correlation, with additional steps that involve well-understood, routine, conventional activity previously engaged in by researchers in the field is not patent-eligible, regardless of whether the steps result in a transformation. On the other hand, reaching back to Neilson, the Court pointed to an eligible process that included not only a law of nature (hot air promotes ignition) but also several unconventional steps involving a blast furnace) that confined the claims to a particular, useful application of the principle. For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments:
With reference to the rejection of claims under 35 USC 101, the Applicant’s arguments were found unpersuasive. The Applicant’s arguments drawn to treating schizophrenia by administering iloperidone, have been fully considered and found unpersuasive. The claims as presented are not drawn to a treatment method and the amendment reciting ‘wherein the detecting identifies a subject for administration of an ESCC therapy do not make the claims eligible subject matter under 101 statute because said limitations are considered as intended use of the method that are not given any patentable weight as a treatment method. Further the claims as presented correlate the presence of methylation of one more gene markers with the disease, which is considered as a law of nature, a judicial exception. For all the above the rejection has been maintained and restate to include amended claim 22 and new claims 41-45 (renumbered as 37-41).
New Rejections necessitated by the amendment
Claim Rejections - 35 USC § 102
9. 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, 5, 8, and renumbered claims 37 and 39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Weilin et al. (Clinical Epigenetics, Vo. 9:129, page 1-12, (2017)).
Weilin et al. teach a method of claim 1, 37, 39, for identifying a subject having esophageal squamous cell carcinoma (ESCC) comprising the steps of
a) extracting genomic DNA from a sample obtained from the subject (page 9, paragraphs under the subheading ‘patients, samples and DNA’ and ‘targeted bisulfite sequencing assay’);
b) performing a conversion reaction on the genomic DNA invitro to convert unmethylated cytosine to uracil by deamination (page 9, paragraphs under the subheading ‘targeted bisulfite sequencing assay’); and
c) detecting nucleic acid methylation of one or more genes in the converted genomic DNA wherein detecting identifies the subject as having ESCC, wherein the one or more genes comprise ZNF542 and one or more genes comprise cg20655070 (page 9, paragraphs under the subheading ‘patients, samples and DNA’ and ‘targeted bisulfite sequencing assay’ and ‘statistical analysis and machine learning’, page 8, paragraph under subheading ‘conclusion’, page 2-7, paragraphs under subheading ‘Results’, table 2-4, : indicating cg20655070 and ZNF542 gene methylation).
With reference to claim 5, Weilin et al. teach that the method comprises PCR (page 8-9, paragraphs under the subheading ‘methods’).
With reference to claim 8, Weilin et al. teach that the sample is a cell sample (page 2-3, paragraphs under results section, page 8-9, paragraphs under the subheading ‘methods’). For all the above the claims are anticipated.
Claim Rejections - 35 USC § 103
10. 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 1, 5-10, 22, 29 and renumbered claims 37-41 are rejected under 35 U.S.C. 103 as being unpatentable over Weilin et al. (Clinical Epigenetics, Vo. 9:129, page 1-12, (2017)) in view of Lleras et al. (The American Journal of Pathology, Vol. 178(5), p. 1965-1974, (2011)) and Lisa et al. (Cancer Prev Res., Vol. 1(5), page 357-367, (2008)).
Weilin et al. teach a method for identifying a subject as having ESCC as discussed above.
However, Weilin et al. did not teach methylation of ZNF132 and quantitative PCR, retrieval of sample using swallowable sponge and endoscopy and bead-based DNA extraction of methylation modification.
Lleras et al. teach a method for identifying oropharyngeal squamous cell carcinoma (OPSCC) comprising detecting methylation of gene markers, wherein the gene markers comprise zinc finger protein genes situated on chromosome 19q13 and detecting chromosomal distribution of differentially methylated CpG loci using quantitative PCR and microarray analysis, the method identified highest overall number of differentially methylated CpG loci on chromosome 19 in OPSCC patient samples and chromosome 19 specific hypermethylated CpG loci comprise ZNF132 and ZNF542 (paragraphs under subheading ‘quantitative real-time PCR’ on page 1967 and paragraphs under subheading ‘chromosomal distribution of differentially methylated CpG loci’ on page 1968).
Lisa et al. teach a method for detecting ESCC in a patient comprising; performing endoscopy, retrieving sample using swallowable sponge (balloon cytology specimen), bead-based extraction of DNA and bisulfite modification and performing quantitative real-time PCR (qPCR) (page 358-359, paragraphs under ‘materials and methods’ section, page 357, paragraph 1 on the right-hand side column).
It would be prima facie obvious to an ordinary person having skilled in the art before the effective filing date of the invention to modify the method of Weilin et al. with zinc finger gene markers as taught by Lleras et al. and sample retrieval and analysis of methylation as taught by Lisa et al. to improve the sensitivity of the method for detecting ESCC in a sample. The ordinary person skilled in the art would have motivated to modify the method of Weilin et al. with Zinc Finger gene ZNF132 as taught by Lleras et al. and sample retrieval and analysis of methylation as taught by Lisa et al. and have a reasonable expectation of success that the combination would improve the sensitivity of the detection method because Lleras et al. teach detecting methylation of zinc finger genes on chromosome 19q13 comprising ZNF542, ZNF132, wherein Lleras et al. explicitly taught hypermethylated genes on chromosome 19 comprising genes ZNF542, ZNF132, wherein ZNF542and ZNF13 are in hypermethylated locus (paragraphs under subheading ‘chromosomal distribution of differentially methylated CpG loci’ on page 1968) and Lisa explicitly taught performing endoscopy , sample retrieval, bead-based DNA extraction of bisulfite treatment and analyzing by quantitative PCR (page 358-359, paragraphs under ‘materials and methods’) such a modification of the method is considered obvious over the cited prior art.
Conclusion
No claims are allowable.
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.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681