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 May 14, 2026 is acknowledged.
Status of the Application
2. Claims 41, 45 and 47-48 are pending under examination. Claims 1-40, 42-44, 46 and 49-85 are canceled. The Applicant’s arguments and the amendment have been fully considered and found persuasive in-part for the following reasons.
Objection to the informalities-Withdrawn
3. The objection to informalities has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 102-Withdrawn
4. The rejection of claims under 35 USC 102(a)(1) as being anticipated by Laird et al. has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 102-Maintained
5. 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 41, 45 and 47-48 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Barany et al. (WO 2016/057832).
Note: Claims recite alternate language ‘or’, which indicates any one of the alternatives.
Barany et al. teach a method of claim 41, diagnosing or prognosing comprising (a) a disease state of cells or tissue based on identifying the presence or level of a plurality of disease-specific nucleic acid markers in a biological sample of an individual, wherein the plurality of markers is in a set comprising 6-12 markers, wherein the markers include methylation markers (para 0220-0221, 0243: indicating 5 to 6 positive markers out of 24 markers tested for colorectal cancers and >5 of 24-48 markers positive for cancer), wherein said method comprises:
obtaining a biological sample from cell-free DNA or RNA originating from the cells or tissue, wherein the biological sample is blood or serum (para 0223, 0379, 630-0639);
fractionating the sample into one or more fraction, said fraction comprises cell-free DNA or exosomes (0223-0225, 0630-0639);
subjecting nucleic acid molecules in said fraction to a bisulfite treatment under conditions suitable to convert unmethylated cytosine residues to uracil residues (0223-0225, 0630-0639);
carrying out at least two enrichment steps for 50% or more markers, wherein for DNA markers, one step comprises selectively amplifying bisulfite-converted DNA methylation markers, while suppressing amplification of the target regions containing wild-type sequences or bisulfite-converted unmethylated sequences (para 0331-0242, 0285-0289, 0379-0384);
applying a first diagnostic step to the biological sample comprising performing one or more assays to detect and distinguish the plurality of markers, thereby identifying their presence or levels in the sample (para 0241, para 0220-0222, 0243, 0287-0295, 0308-0320, 0482-0489); and
applying a second diagnostic step to samples from those individuals identified in the first diagnostic step as more likely than a reference population to be diagnosed or prognosed with a cancer disease state, wherein the second diagnostic step comprising performing one or more assays to detect and distinguish the plurality of disease-specific markers, thereby identifying their presence or levels in the biological sample, wherein the plurality of markers used in the second diagnostic step at least one marker that is not used in the first diagnostic step (para 0241, para 0220-0222, 0243, 0287-0295, 0308-0320, 0482-0489, 0639-0656);
wherein individuals are diagnosed or prognosed with the disease state of cells or tissue after applying the second diagnostic step if a minimum of 2 or 3 markers are present or are above a cutoff level in a marker set comprising from 6-12 or 24-48 markers (para 0220-0221, 0640-0656, 0378).
With reference to claim 45, 48, Barany et al. teach that the present or cutoff level in >66% or >95% of biological samples of a given cancer tissue from individuals diagnosed with a given solid tissue cancer and comparing samples from disease with normal individual, wherein marker Ct value is >2 (para 0220-0221).
With reference to claim 47, Barany et al. teach that the one or more assays to detect and distinguish the plurality of disease or cell/tissue specific DNA comprises qPCR, RT-PCR, digital PCR, a bisulfite dPCR, ligation (para 0604-0639). For all the above the claims are anticipated.
Response to Arguments:
With reference to the rejection of claims under 35 USC 102(a)(1) as being anticipated by Barany et al., the Applicant’s arguments and the amendment have been fully considered and found unpersuasive. Because Barany et al. teach second diagnostic assay (para 0220-0222, 0243, 0287-0295, 0308-0320, 0482-0489), wherein the second diagnostic assay does not comprise at least one marker present in the first diagnostic assay (para 0381-0382, 0640-0656 (control unmethylated HgDNA) as amended and the rejection has been maintained and restated to address the amendment.
Claim Rejections - 35 USC § 101-Maintained
6. 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 41, 45 and 47-48 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claims 41, 45, 47-48 recite a method of diagnosis or prognosis of a disease based on a set of DNA markers, a process, statutory category. Claims 41, 45, 47-48 recite a judicial exception (law of nature, natural phenomenon) because claims recite a correlation of the presence of a set of markers with a disease in a subject, or with colorectal cancer, which is a law
of nature or natural phenomenon that exits in nature. The claims do not include any additional elements that are sufficient to amount for significantly more than the judicial exception because the additional steps (bisulfite treatment, enriching, amplifying, quantitating) which 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 (US 2018/0265917; US 2014/0093873; Barany et al. (WO 2016/057832). 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. This judicial exception is not integrated into a practical application because the judicial exception is not markedly different from the natural phenomenon because the claims recite the abstract idea of determining by a computer processing. It is noted that a judicial exception itself, such as law of nature phenomenon, cannot be considered to meet the criteria of "significantly more" than a judicial exception. 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 long standing exceptions (laws of nature, natural phenomena, and abstract ideas) to categories of patent eligibility defined in 35 U.S.C. § 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 all the above, the claims are rejected under 35 USC 101.
Response to Arguments:
With reference to the rejection of claims under 35 USC 101, the Applicant’s arguments and the amendment have been fully considered and found unpersuasive. With reference to the Applicant’s arguments drawn to bisulfite treatment and enrichment step as amended, the arguments have been found unpersuasive because as discussed in the rejection applying routine or conventional steps in the claims do not add anything to transform the method to significantly more to modify the correlation of the marker levels to a disease state in a solid-tissue cancer. Further, combinatorial model is not transforming the method to a significantly more because applying said combinatorial model represents an abstract idea and mental step to derive at the correlation of said marker levels with a disease state, wherein said correlation exists in nature. For all the above the rejection has been maintained and restated to address the amendment.
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. 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
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