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 specie election without traverse of Claim 2 in the reply filed on 03/13/2026 is acknowledged. Claims 1-4 read upon the elected specie.
Claims 5-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected specie of claim 5, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/13/2026.
Claims Status
Claims 1-7 are pending.
Claims 5-7 are withdrawn.
Claims 1-4 are currently under examination.
Priority
This application is a Continuation of International Application No. PCT/JP2022/006737, filed February 18, 2022, which claims priority to Japanese Patent Application No. 2021-028913, filed February 25, 2021.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Japan on February 25, 2021. It is noted, however, that applicant has not filed a certified copy of the JP 2021-028913 application as required by 37 CFR 1.55. An English translation of the foreign application JP 2021-028913 is required for the record to be considered for the priority date of February 25, 2021. Furthermore, please check accuracy of the claimed foreign priority. Accordingly, the priority date of claim set filed on July 24, 2023, is determined to be February 18, 2022.
Specification
The disclosure is objected to because of the following informalities: disclosure includes claim to foreign priority of Japanese Patent Application No. 2021-028913, filed February 25, 2021on Pg. 1, which does not appear to be within the scope of the instant application. Appropriate correction is required.
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 2-4 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 2 is indefinite over the limitation “wherein when a disease onset or progression of which correlates with unmethylation of the gene is the target disease, the bisulfite reagent is a bisulfite reagent which has been evaluated by the method according to claim 1 as having a failed conversion tendency”. It is unclear whether failed conversion tendency is required for disease onset or progression correlated to unmethylated gene or if the disease onset or progression correlated to an unmethylated gene is an analysis based on the consequence of the failed conversion tendency. Claims 3-4 depend on claim 2.
Claim 2 is indefinite over the limitation “wherein when a disease onset or progression of which correlates with methylation of the gene is the target disease, the bisulfite reagent is a bisulfite reagent which has been evaluated by the method according to claim 1 as having an inappropriate conversion tendency”. It is unclear whether inappropriate conversion tendency is required for disease onset or progression correlated to methylation gene or if the disease onset or progression correlated to an methylation of the gene is an analysis based on the consequence of the inappropriate conversion tendency. Claims 3-4 depend on claim 2.
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 1-4 are rejected under 35 U.S.C. 101 because the claimed invention is directed towards abstract ideas of mathematical concepts-calculating an error rate and mental processes-comparing error rate and estimating false positive and false negative rate and routine and conventional steps of preparing a DNA sample, treating a DNA sample with a bisulfite reagent, and measuring degree of methylation, without significantly more. The claim(s) recite(s) abstract ideas and routine and conventional methods. This judicial exception is not integrated into a practical application because no additional elements integrate the judicial exceptions into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional elements are considered significantly more than the judicial exceptions.
Claim analysis
The instant claim 1 is directed towards: A method of evaluating a bisulfite reagent, the method comprising the following (a) to (c): (a) preparing a DNA sample 1 in which a CpG site to be measured is not methylated, treating the DNA sample 1 with a bisulfite reagent to be evaluated, and subsequently measuring a degree of methylation of the CpG site to be measured to calculate an error rate 1, where the error rate 1 is an average value of the degree of methylation of the CpG site to be measured; (b) preparing a DNA sample 2 which has the same sequence as the DNA sample 1 and in which the CpG site to be measured is methylated, treating the DNA sample 2 with the bisulfite reagent to be evaluated, and subsequently measuring a degree of methylation of the CpG site to be measured to calculate an error rate 2, where the error rate 2 is calculated by 100 - (an average value of the degree of methylation of the CpG site to be measured) and (c) comparing the error rate 1 with the error rate 2, wherein when a relationship of the error rate 1 ≤ the error rate 2 is satisfied, the bisulfite reagent is evaluated as having an inappropriate conversion tendency, and wherein when a relationship of the error rate 1 > the error rate 2 is satisfied, the bisulfite reagent is evaluated as having a failed conversion tendency.
The calculate an error rate 1 is considered to be an abstract idea.
The error rate 1 is an average value of the degree of methylation is considered to be an abstract idea.
The calculate an error rate 2 is considered to be an abstract idea.
The error rate 2 is calculated by 100 - (an average value of the degree of methylation of the CpG site to be measured) is considered to be an abstract idea.
The comparing the error rate 1 with the error rate 2 is considered to be an abstract idea.
The wherein when a relationship of the error rate 1 ≤ the error rate 2 is satisfied, the bisulfite reagent is evaluated as having an inappropriate conversion tendency is considered to be an abstract idea.
The wherein when a relationship of the error rate 1 > the error rate 2 is satisfied, the bisulfite reagent is evaluated as having a failed conversion tendency is considered to be an abstract idea.
The steps of preparing a DNA sample, treating a DNA sample with a bisulfite reagent, and measuring degree of methylation are considered to be active step. The active steps are routine and conventional as demonstrated by the 35 USC § 103 rejections stated below.
Dependent claims set forth further limitations about a method of a genetic test comprising determining a methylation status of gene correlation to disease onset or progress using a bisulfite reagent evaluated by the method of claim 1, estimation of false positive and false negative rate.
The instant claim 2 is directed towards: A method of a genetic test which analyzes a degree of methylation of a gene of a subject who has no history of illness in regard to a target disease onset or progression of which correlates with methylation or unmethylation of the gene, the method comprising treating DNA of the subject with a bisulfite reagent, wherein when a disease onset or progression of which correlates with methylation of the gene is the target disease, the bisulfite reagent is a bisulfite reagent which has been evaluated by the method according to claim 1 as having an inappropriate conversion tendency, and wherein when a disease onset or progression of which correlates with unmethylation of the gene is the target disease, the bisulfite reagent is a bisulfite reagent which has been evaluated by the method according to claim 1 as having a failed conversion tendency.
The evaluated by the method according to claim 1 is considered to be an abstract idea.
The treating DNA of the subject with a bisulfite reagent is considered to be active step. The active step is routine and conventional as demonstrated by the 35 USC § 103 rejections stated below.
The instant claim 3 is directed towards: The method according to claim 2, wherein a false positive rate and a false negative rate in the test are estimated from values of the error rate 1 and the error rate 2 in the evaluation of the bisulfite reagent.
The false positive rate and a false negative rate in the test are estimated from values of the error rate 1 and the error rate 2 in the evaluation of the bisulfite reagent is considered to be an abstract idea.
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case, the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, abstract ideas.
With regard to claim 1, the claim recites “A method of evaluating a bisulfite reagent, the method comprising the following (a) to (c): (a) preparing a DNA sample 1 in which a CpG site to be measured is not methylated, treating the DNA sample 1 with a bisulfite reagent to be evaluated, and subsequently measuring a degree of methylation of the CpG site to be measured to calculate an error rate 1, where the error rate 1 is an average value of the degree of methylation of the CpG site to be measured; (b) preparing a DNA sample 2 which has the same sequence as the DNA sample 1 and in which the CpG site to be measured is methylated, treating the DNA sample 2 with the bisulfite reagent to be evaluated, and subsequently measuring a degree of methylation of the CpG site to be measured to calculate an error rate 2, where the error rate 2 is calculated by 100 - (an average value of the degree of methylation of the CpG site to be measured) and (c) comparing the error rate 1 with the error rate 2, wherein when a relationship of the error rate 1 ≤ the error rate 2 is satisfied, the bisulfite reagent is evaluated as having an inappropriate conversion tendency, and wherein when a relationship of the error rate 1 > the error rate 2 is satisfied, the bisulfite reagent is evaluated as having a failed conversion tendency.” The calculate an error rate 1 and error rate 2 are considered to be an abstract ideas. The average value of the degree of methylation is considered to be an abstract idea. The error rate 2 is calculated by 100 - (an average value of the degree of methylation of the CpG site to be measured) is considered to be an abstract idea. The comparing the error rate 1 with the error rate 2 is considered to be an abstract idea. The relationship of the error rate 1 ≤ the error rate 2 is an abstract idea. The evaluated as having an inappropriate conversion tendency is considered to be an abstract idea. The relationship of the error rate 1 > the error rate 2 is an abstract idea. The evaluated as having a failed conversion tendency is considered to be an abstract idea. The steps of preparing a DNA sample, treating a DNA sample with a bisulfite reagent, and measuring degree of methylation are considered to be routine and conventional.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? No, there are no additional steps that integrate the claims into a practical application.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No, there are no additional elements that are significantly more than the judicial exceptions.
Regarding claim 1, the claim requires the routine and conventional active steps of The steps of preparing a DNA sample, treating a DNA sample with a bisulfite reagent, and measuring degree of methylation similar to that of Genereux et al. (“Genereux”; (2008). Errors in the bisulfite conversion of DNA: modulating inappropriate- and failed-conversion frequencies. Nucleic acids research, 36(22), e150.).
Genereux discloses “Bisulfite treatment can be used to ascertain the methylation states of individual cytosines in DNA. Ideally, bisulfite treatment deaminates unmethylated cytosines to uracils, and leaves 5-methylcytosines unchanged. Two types of bisulfite-conversion error occur: inappropriate conversion of 5-methylcytosine to thymine, and failure to convert unmethylated cytosine to uracil. Conventional bisulfite treatment requires hours of exposure to low-molarity, low-temperature bisulfite (‘LowMT’) and, sometimes, thermal denaturation. An alternate, high-molarity, high-temperature (‘HighMT’) protocol has been reported to accelerate conversion and to reduce inappropriate conversion. We used molecular encoding to obtain validated, individual-molecule data on failed- and inappropriate-conversion frequencies for LowMT and HighMT treatments of both single-stranded and hairpin-linked oligonucleotides. After accounting for bisulfite-independent error, we found that: (i) inappropriate-conversion events accrue predominantly on molecules exposed to bisulfite after they have attained complete or near-complete conversion; (ii) the HighMT treatment is preferable because it yields greater homogeneity among sites and among molecules in conversion rates, and thus yields more reliable data; (iii) different durations of bisulfite treatment will yield data appropriate to address different experimental questions; and (iv) conversion errors can be used to assess the validity of methylation data collected without the benefit of molecular encoding.” (Abstract).Thus, the claim does not provide additional steps which are significantly more.
Dependent claims require a method of a genetic test comprising determining a methylation status of gene correlation to disease onset or progress using a bisulfite reagent evaluated by the method of claim 1, estimation of false positive and false negative rate which include additional abstract ideas and steps that are routine and conventional based on Genereux et al. (“Genereux”; (2008). Errors in the bisulfite conversion of DNA: modulating inappropriate- and failed-conversion frequencies. Nucleic acids research, 36(22), e150.) in view of Lan et al. (“Lan”;. (2019). An Internal Control for Evaluating Bisulfite Conversion in the Analysis of Short Stature Homeobox 2 Methylation in Lung Cancer. Asian Pacific journal of cancer prevention : APJCP, 20(8), 2435–2443..
Claim Rejections - 35 USC § 103
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Genereux et al. (“Genereux”; (2008). Errors in the bisulfite conversion of DNA: modulating inappropriate- and failed-conversion frequencies. Nucleic acids research, 36(22), e150.)
Genereux discloses “Bisulfite treatment can be used to ascertain the methylation states of individual cytosines in DNA. Ideally, bisulfite treatment deaminates unmethylated cytosines to uracils, and leaves 5-methylcytosines unchanged. Two types of bisulfite-conversion error occur: inappropriate conversion of 5-methylcytosine to thymine, and failure to convert unmethylated cytosine to uracil. Conventional bisulfite treatment requires hours of exposure to low-molarity, low-temperature bisulfite (‘LowMT’) and, sometimes, thermal denaturation. An alternate, high-molarity, high-temperature (‘HighMT’) protocol has been reported to accelerate conversion and to reduce inappropriate conversion. We used molecular encoding to obtain validated, individual-molecule data on failed- and inappropriate-conversion frequencies for LowMT and HighMT treatments of both single-stranded and hairpin-linked oligonucleotides. After accounting for bisulfite-independent error, we found that: (i) inappropriate-conversion events accrue predominantly on molecules exposed to bisulfite after they have attained complete or near-complete conversion; (ii) the HighMT treatment is preferable because it yields greater homogeneity among sites and among molecules in conversion rates, and thus yields more reliable data; (iii) different durations of bisulfite treatment will yield data appropriate to address different experimental questions; and (iv) conversion errors can be used to assess the validity of methylation data collected without the benefit of molecular encoding.” (Abstract).
Regarding claim 1 Steps (a-b), Genereux teaches a method comprising “a DNA substrate with which to measure conversion-error frequencies, we designed and ordered from GeneLink, Hawthorne, NY four single-stranded synthetic oligonucleotides. Two of these, methylated top strand (‘TM’) and methylated bottom strand (‘BM’), contained 5-methylcytosine at all 10 of their CpG sites” (Pg. 3, Methods- Design and assembly of molecularly encoded oligonucleotides) and “The other two oligonucleotides, (‘TU’), unmethylated top strand, and (‘BU’), unmethylated bottom strand, were identical in sequence to TM and BM, except that they contained cytosines at the sites that were occupied by 5-methylcytosine in TM and BM.” (Pg. 3, Methods- Design and assembly of molecularly encoded oligonucleotides). Genereux teaches a method comprising “In preparation for HighMT treatment, molecularly encoded oligonucleotides (20 μl) were first denatured in 0.3 N NaOH at 42°C for 20 min, added to the HighMT bisulfite solution (180 μl), and held at 70°C for durations ranging from 5 to 200 min.” (Pg. 4, Methods- Bisulfite treatment of molecularly encoded oligonucleotides). Genereux teaches a method comprising “PCR products were cycle-sequenced using either the T7 primer or the M13R primer, and Big-Dye Terminator v3.1 (ABI, Foster City, CA), then sequenced on an ABI3100, using a 36 cm POP6 array (Comparative Genomics Center, University of Washington, Seattle, WA).” (Pg. 4, Methods- Post-bisulfite cleanup, PCR amplification and sequencing) and “DNA sequencing is a standard component of protocols designed to collect DNA methylation patterns. To investigate how often errors were introduced during the sequencing and base-calling processes, we performed repeat sequencing on a subset of our clones”. Genereux teaches a method comprising “we calculated point estimates as the number of events divided by the number of opportunities.” (Pg. 4, Methods- Data analysis). Genereux teaches a method comprising “we examined both population-mean and single-molecule error frequencies for single-stranded … molecules treated under the LowMT and HighMT conditions” (Pg. 8, Investigating bisulfite-conversion error by analysis of individual molecules; Fig. 4 ;Table 3). Genereux teaches a method comprising the proportions of error frequencies: failed conversions (%) and inappropriate conversions (%) due to changes in conditions such as the molar concentrations of components in a bisulfite reagent, the reaction time, the reaction temperature, the substrate structure, etc. were confirmed. Thus, Genereux suggests a method comprising step (a) preparing a DNA sample 1 in which a CpG site to be measured is not methylated, treating the DNA sample 1 with a bisulfite reagent to be evaluated, and subsequently measuring a degree of methylation of the CpG site to be measured to calculate an error rate 1, where the error rate 1 is an average value of the degree of methylation of the CpG site to be measured and (b) preparing a DNA sample 2 which has the same sequence as the DNA sample 1 and in which the CpG site to be measured is methylated, treating the DNA sample 2 with the bisulfite reagent to be evaluated, and subsequently measuring a degree of methylation of the CpG site to be measured to calculate an error rate 2, where the error rate 2 is calculated by 100 - (an average value of the degree of methylation of the CpG site to be measured)
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Regarding claim 1 Step (c), Genereux teaches a method wherein the error frequencies of failed conversions and inappropriate conversions in a bisulfite reaction were compared (Tables 3-5.). Table 3 illustrates the relationship of error rate 1 ≤ the error rate 2 in the error frequencies of table rows indicated by HighMT 80 min and HighMT 200 min (Table 3), where the bisulfite treatment is shown to have primarily inappropriate conversion errors. Genereux teaches a method comprising “inappropriate-conversion events detected in the 200 min sample occurred primarily during the last 120 minutes of bisulfite treatment on molecules that had already achieved complete conversion” (Pg. 8, Single-stranded DNA treated under the HighMT protocol). Table 3 also illustrates the relationship of error rate 1 > the error rate 2 in error frequencies of table rows indicated by HighMT 5 min, HighMT 15 min and HighMT 30 min (Table 3), where the bisulfite treatment is shown to have primarily failed conversion errors. Thus, Genereux suggests a method comprising step (c) comparing the error rate 1 with the error rate 2, wherein when a relationship of the error rate 1 ≤ the error rate 2 is satisfied, the bisulfite reagent is evaluated as having an inappropriate conversion tendency, and wherein when a relationship of the error rate 1 > the error rate 2 is satisfied, the bisulfite reagent is evaluated as having a failed conversion tendency.
Therefore, the invention as recited in claim 1 is prima facie obvious over the prior art Genereux et al. One of ordinary skill in the art would have had a reasonable expectation of success given the obviousness of the claim limitations, which were already known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective function. Thus, it would have been obvious to provide a method of evaluating a bisulfite reagent according to the limitations of the instant application claim 1 based on Genereux et al..
Claim 1-4 is rejected under 35 U.S.C. 103 as being unpatentable over Genereux et al. (“Genereux”; (2008). Errors in the bisulfite conversion of DNA: modulating inappropriate- and failed-conversion frequencies. Nucleic acids research, 36(22), e150.) in view of Lan et al. (“Lan”;. (2019). An Internal Control for Evaluating Bisulfite Conversion in the Analysis of Short Stature Homeobox 2 Methylation in Lung Cancer. Asian Pacific journal of cancer prevention : APJCP, 20(8), 2435–2443.
The teachings of Genereux are documented above in the rejection of claim 1 under 35 U.S.C. 103. Claim 2 depends on claim 1. Claims 3 and 4 depend on claim 2, which depends on claim 1. Genereux does not explicitly teach all of the limitations of claims 2-4.
Genereux discloses “The methylation status is considered as powerful diagnostic, prognostic, and predictive biomarkers. However, the limited DNA amount and conversion efficiency after bisulfite treatment are considerable hindrances in quantitative methylation analysis. In this study, we designed an artificial internal control (IC) system that contained the cytosine-free fragment (CFF) following CpG sequences of the SHOX2 promoter whose methylation status has been described as a valuable biomarker of lung cancer. Its performance in quantifying DNA recovery and bisulfite conversion efficiency as well as in detecting false-positive SHOX2 methylation was determined on samples from lung cancer patients.” (Abstract-Objective).
Interpretation: Regarding claim 2, “A method of a genetic test which analyzes a degree of methylation of a gene of a subject who has no history of illness in regard to a target disease onset or progression of which correlates with methylation or unmethylation of the gene” is interpreted as a preamble.
Regarding claim 2, Lan teaches a method wherein “Lymphocytes were collected from healthy volunteers; formalin-fixed, paraffin-embedded (FFPE) tissue specimens were collected from 97 lung cancer patients… Genomic DNAs were extracted from lymphocytes of healthy volunteers or FFPE lung tissues… DNAs quantified with the NanoDrop2000 (Invitrogen) was submitted to bisulfite conversion using the EpiTect Bisulfite Kit (Qiagen)” (Pg. 2437, Sample collection, genomic DNA isolation and bisulfite conversion). Thus, Genereux and Lan suggest a method comprising treating DNA of the subject with a bisulfite reagent.
Regarding claim 2, Lan teaches a method wherein “SHOX2 gene promoter whose methylation status has been described as a valuable biomarker for lung cancer detection” (Pg. 2436 , Introduction). Lan teaches a method wherein “different commercial bisulfite conversion kits, applied to various DNA sources with high and low molecular weight (HMW/LMW), have been comprehensively evaluated for their DNA recovery and bisulfite conversion efficiencies” (Pg. 2436, Introduction). Lan also teaches “Subsequently, based on the bisulfite conversion efficiency assessed on the IC, false positive SHOX2 methylation level and successful conversion of the SHOX2 sequence was accurately detected in patients with lung cancer patients” (Pg. 2436, Introduction) Genereux teaches a method wherein “For experiments where even a very small number of methylated cytosines would provide important biological information, it will be desirable to minimize the misclassification of unmethylated cytosines as methylated... For experiments where even a very small number of unmethylated cytosines would provide important biological information, it will generally be desirable to minimize the number of inappropriate-conversion events… To assess whether complete or near-complete methylation really does occur in some biological cases, or whether it is instead an artifact of conversion error, it is necessary to choose conditions that yield low inappropriate-conversion frequencies. For this goal, too, HighMT conditions seem preferable. Specifically, our data indicate that for our single-stranded oligonucleotide treated under HighMT conditions, durations of ∼50–80 min would yield successful conversion frequencies between 98% and 99.9%, with few or no inappropriate-conversion events.” (Pg. 15, Modulating bisulfite-conversion error frequencies to address a specific biological question). Thus, Genereux and Lan suggest a method wherein when a disease onset or progression of which correlates with methylation of the gene is the target disease, the bisulfite reagent is a bisulfite reagent which has been evaluated by the method according to claim 1 as having an inappropriate conversion tendency, and wherein when a disease onset or progression of which correlates with unmethylation of the gene is the target disease, the bisulfite reagent is a bisulfite reagent which has been evaluated by the method according to claim 1 as having a failed conversion tendency.
Regarding claim 3, Genereux teaches that “When inappropriate conversion occurs and is ignored in data analysis, it will lead to underestimates of genomic methylation densities. In contrast, when inappropriate conversion occurs and its frequency is known, it can be included as a parameter in the data analysis. Information on failed- and inappropriate-conversion frequencies is therefore essential for inference from detailed DNA methylation patterns.” (Pg. 2, Introduction). Thus, Genereux and Lan suggest a method wherein a false positive rate and a false negative rate in the test are estimated from values of the error rate 1 and the error rate 2 in the evaluation of the bisulfite reagent.
Regarding claim 4, Lan teaches a method wherein “lung cancer” (Pg. 2437, Sample collection, genomic DNA isolation and bisulfite conversion). Lan teaches a method wherein “biomarker for lung cancer detection” (Pg. 2436 , Introduction). Thus, Genereux and Lan suggest a method wherein the disease is cancer.
Genereux and Lan are both considered to be analogous to the claimed invention because they are in the same field of evaluating bisulfite conversion. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods of method of evaluating a bisulfite reagent according to the limitations of the instant application claim 1 as taught by Genereux to incorporate the method of treating DNA of a subject with a bisulfite reagent and wherein the methylation status of gene correlates with disease, and wherein the disease is cancer as taught by Lan and provide a method for analyzing the degree of methylation of a gene in a subject. These claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome according to the limitations of claims 2-4. Doing so would allow for enhanced accuracy of methylation conversions.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's
disclosure: Holmes, E. E., Jung, M., Meller, S., Leisse, A., Sailer, V., Zech, J., Mengdehl, M., Garbe, L. A., Uhl, B., Kristiansen, G., & Dietrich, D. (2014). Performance evaluation of kits for bisulfite-conversion of DNA from tissues, cell lines, FFPE tissues, aspirates, lavages, effusions, plasma, serum, and urine. PloS one, 9(4), e93933. (entire document-evaluating bisulfite reagent) Claim 1 and 2 (in part).
Patent App. No. WO 2008103761 A2, Aug. 28, 2008 (Pg. 3, methylation of gene and cancer diagnosis; Pg. 89-91 and 99, Bisulfite treatment, Pg. 104 methylation conversion error) Claims 2-4 (in-part).
No claims are in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KENDRA R VANN-OJUEKAIYE whose telephone number is (571)270-7529. The examiner can normally be reached M-F 9:00 AM- 5:00 PM.
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/KENDRA R VANN-OJUEKAIYE/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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