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. Applicant’s election without traverse of Group 10 in the reply filed on November 13, 2025 is acknowledged.
Status of the Application
2. Claims 41 45, 47 and 48 in-part with cell/ tissue-specific DNA markers are considered for examination. The election of group I species has been considered. Claims 1-7, 17-22, 46, 49-50, 56, 62, 68, 74 and 80 are withdrawn from further consideration as being drawn to non-elected group. Claims 8-16, 23-40, 42-44, 51-55, 57-61, 63-67, 69-73, 79-79 and 81-85 were canceled.
Priority
3. This application filed on November 03, 2021 is a 371 of PCT/US20/31044 filed on May 01, 2020 which claims a priority benefit of US 62/843,032 filed on May 03, 2019.
Informalities
4. The disclosure is objected for the following informalities:
Claim 41 recites “n”. Removing the ‘’ ‘’ marks is suggested.
Claim 48 recites the disease vs. normal individual. Removal of full stop after vs is suggested.
Claim Interpretation
5. Claim 41 recites step a) or b) or c)- which requires either a) b), or c) not necessarily require all steps a), b) and c). Claim 41 further recites’ one or more’. In the following rejections step a) or b) and one of the alternatives is considered as meeting the limitations in the claim.
Claim Rejections - 35 USC § 102
6. 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.
A. Claims 41, 45, 47-48 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Laird et al. (US 2012/0219946).
Laird et al. Teach a method of claim 41, 45, diagnosing or prognosis comprising a) or b) identifying the presence or level of a plurality of disease-specific and/or cell/tissue-specific DNA markers in a biological sample of an individual, wherein the plurality of markers in a set comprises 6-12 or more markers wherein disease is colorectal cancer (para 0013-0016, 0021-0029, 0079-0080, 0268-0279, 0286-0294: indicating 3 to 5 positive markers from a panel of 14 genomic markers or more);
wherein for a), or b) each marker in a given set present, or above a cutoff (threshold or cutoff) level in >50% of biological samples comprising cells; present, wherein at least 50% of the markers in a set comprise one or more methylated residues, obtaining a biological sample including cell-free DNA, wherein the biological sample comprises cells, serum, blood or plasma (para, 0013-0016, 0021-0026, 0034, 0079-0080, 0101-111, 0187-0189);
fractionating (extracting) the sample in one or more fractions, wherein at least one fraction (extracted sample) comprises cell-free DNA (circulating DNA) (para 0189, 0105-0111)
subjecting nucleic acid molecules in one or more fractions to a bisulfite treatment under conditions suitable to convert unmethylated cytosine residues to uracil residues (para 0106-0111, 0076-0083, 0190-0192):
carrying out at least two enrichment steps for disease specific or tissue-specific DNA markers by carrying out nucleic acid amplification step and performing one or more assays to detect and distinguish the plurality of disease-specific or cell/ tissue specific markers, thereby identifying their presence or levels in the sample (para 0082-0111, 0193-0200, 0228-0229, 0268-0279);
wherein for step a) or b) individuals are diagnosed or prognosed with the disease state of the cells or tissue, 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 more (para 0079-0080, 0105-0111).
With reference to claim 47, Laird et al. teach that the one or more assays to detect and distinguish the plurality of disease or cell/tissue specific DNA comprises bisulfite PCR, qPCR, mass spectrometry and hybridization assays (para 0081-0111, 0193-0210, 0228-0229, 0267-0279).
With reference to claim 48, Laird et al. teach that the one or more cutoff levels of one or more assays to detect comprise one or more of comparison and determination in the one or more marker assays comparing samples from the disease vs normal individual marker ratio of detected marker-signal > 1.5 (para 0024-0026, 0034-0036, 0230-0231, 0267-0268, 0287-0294, table 4). For all the above the claims are anticipated.
B. 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).
Barany et al. teach a method of claim 41, 45, diagnosing or prognosis comprising a) or b) identifying the presence or level of a plurality of disease-specific and/or cell/tissue-specific DNA markers in a biological samples of an individual, wherein the plurality of markers in a set comprises 6-12 or more markers wherein the cancer comprises colorectal cancer (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 the markers include methylation markers);
wherein for a), or b) each marker in a given set present, or above a cutoff (threshold) level in >50% of biological samples comprising cells (para 0220, 0604-0639);
present, wherein at least 50% of the markers in a set comprise one or more methylated residues, obtaining a biological sample including cell-free DNA, wherein the biological sample comprises cells, serum, blood or plasma (para 0223, 630-0639);
fractionating the sample in one or more fractions, wherein at least one fraction comprises cell-free DNA, or exomes (0223-0225, 0630-0639);
subjecting nucleic acid molecules in one or more fractions to a bisulfite treatment under conditions suitable to convert unmethylated cytosine residues to uracil residues (para 0630-0639, 0288-0296, 0301-0316);
carrying out at least two enrichment steps for disease specific or tissue-specific DNA markers by carrying out nucleic acid amplification step and performing one or more assays to detect and distinguish the plurality of disease-specific or cell/ tissue specific markers, thereby identifying their presence or levels in the sample (para 0630-0639, 0214-0219, 0223-0227, 0301-0316: indicating PCR, qPCR digital PCR and LDR amplification assays);
wherein for step a) individuals are diagnosed or prognosed with the disease state of the cells or tissue, 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 more (para 0220-0221, 0604-0639).
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).
With reference to claim 48, Barany et al. teach that the one or more cutoff levels of one or more assays to detect comprise one or more of comparison and determination in the one or more marker assays comparing samples from the disease vs normal individual marker Ct value and ratio of detection signal > 1.5 (para 0604-0636, 0220-0228, indicating Ct value threshold (cutoff)) and signal ratio). For all the above the claims are anticipated.
Claim Rejections - 35 USC § 101
7. 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). 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.
Conclusion
No claims are allowable.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681