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 the claims of Group in the reply filed on 03 is acknowledged. The traversal is on the ground(s) that the species election requirement does not provide sufficient reason or examples to support a conclusion that the species are patentably distinct. This is not found persuasive because the species are directed to structurally and functionally different nucleotide sequences based on various positions on various chromosomes. The traversal is also on the ground(s) that the species election requirement does not provide a sufficient basis to indicate that the examination of more than one species would provide a serious search burden. The traversal continues to assert that restriction is only proper if the claims of the restricted groups are independent or patentably distinct and there would be a serious search and/or examination burden. This is not found persuasive because this is a national stage application filed under 35 U.S.C. 371. The standard for restriction in such an application is a lack of unity determination, which was set forth in the previous office action. Finally, the traversal is also on the ground(s) that the unity of invention does exist between Group I and Group II because there is a technical feature that involves the same special technical feature and these groups, taken as a whole, makes over the prior art. Further, the traversal is on the ground(s) that there was no indication that the content of the claims was interpreted in light of the description when making the assertion of a lack of unity and that the burden to sustain the conclusion that the groups lack of unity of invention has not been met. First it is noted that while the traversal asserts that there is a same special technical feature between Group I and Group II, the traversal does not state what this same special technical feature is. In addition, these assertions were not found persuasive because the lack of unity determination was set forth in the previous office action (see paragraph 5 of previous office action) in which it was determined that even though Group I and Group II had the same technical feature of detection of DNA methylation level of at least one CpG site in a nucleotide sequence, this shared technical feature is not a special technical feature because it does not make a contribution over the prior art cited in the previous office action which teaches detection of methylation levels in a variety of biomarker nucleotide sequences.
The requirement is still deemed proper and is therefore made FINAL.
Group II, claims 5-9, are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction requirement in the reply filed on 03/25/2025.
A first office action on the merits of claims 1-4 & 10-13 with the species elections of position 111,813,690 on chromosome 1 in claims 1 & 10 is set forth herein.
Information Disclosure Statement
Only the abstracts of the references in the IDS submitted on 06/27/2022 that are lined through under, the foreign patent documents section, were considered because an English copy of the full documents were not provided.
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 1-4 & 10-13 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.
Regarding claim 1, the recitation of “from the group consisting of” in line 5 of the claim followed by the recitation of “…position 158,799,777, and position 158,799,789” in lines 4-5 of the claim, “…position 111,813,690, and position 111,813,698” in lines 7-8 of the claim, “…position 28,956,384, and position 28,956,387” in line 9 of the claim, “…position 91,182,528, and position 91,182,534” in line 10 of the claim, “…position 119,535,928, and position 119,535,937” in line 11 of the claim, “…position 4,850,075, and position 4,850,090” in line 12 of the claim, “…position 31,846,839, and position 31,846,833” in lines 13-14 of the claim, “…and position 106,187,192 and position 106,187,210” in line 14 of the claim is unclear. It is unclear if the group is grouped by positional information, i.e. all positions a part of the same group, or if the group is grouped by chromosomal information, i.e. all positions of the same chromosome correspond to the same group. In addition, the recitation of “position 158,799,748 … on chromosome 7… and position 106,187,210 on chromosome 14” in lines 6-15 of the claim is unclear because the claim and the specification does not define what human genome the positions are a part of. It is unclear how to determine what positions are being referred to without the human reference genome that these positions are on. Finally, the recitation of “on the basis of the detected DNA methylation level” in lines 16-17 of the claim is unclear as to which condition is indicative of “determining whether the cell or tissue has upper urinary tract urothelial carcinoma”. Does it require a specific type of methylation to be detected? Does it also encompass when methylation is not detected on the selected CpG site? In addition, the claim and the specification does not define what “on the basis of the detected DNA methylation” encompasses and it is unclear whether the status of a single position on a chromosome will be able to detect “whether a cell or tissue has upper urinary tract carcinoma”.
Regarding claim 3, the recitation of “pyrosequencing method, mass spectrometry” in line 2 of the claim followed by the recitation of “a bead array method or ion exchange chromatography” in lines 2-3 of the claim is unclear. It is unclear if a bead array and ion exchange chromatography are part of the same method performed for detection of the DNA methylation level, or if it is the result of a typographical error and should read “pyrosequencing method, mass spectrometry, a bead array method, or ion exchange chromatography”.
Regarding claim 10, the recitation of “from the group consisting of” in line 5 of the claim followed by the recitation of “…position 158,799,777, and position 158,799,789” in lines 6-7 of the claim, “…position 111,813,690, and position 111,813,698” in lines 7-8 of the claim, “…position 28,956,384, and position 28,956,387” in lines 9-10 of the claim, “…position 91,182,528, and position 91,182,534” in line 10 of the claim, “…position 119,535,928, and position 119,535,937” in lines 11-12 of the claim, “…position 4,850,075, and position 4,850,090” in lines 12-13 of the claim, “…position 31,846,839, and position 31,846,833” in lines 13-14 of the claim, “…and position 106,187,192 and position 106,187,210” in lines 14-15 of the claim is unclear. It is unclear if the group is grouped by positional information, i.e. all positions a part of the same group, or if the group is grouped by chromosomal information, i.e. all positions of the same chromosome correspond to the same group. In addition, the recitation of “position 158,799,748 … on chromosome 7… and position 106,187,210 on chromosome 14” in lines 6-15 of the claim is unclear because the claim and the specification does not define what human genome the positions are a part of. It is unclear how to determine what positions are being referred to without the human reference genome that these positions are on. Finally, the recitation of “on the basis of the detected DNA methylation level” in lines 16-17 of the claim is unclear as to which condition is indicative of “determining whether the cell or tissue has upper urinary tract urothelial carcinoma”. Does it require a specific type of methylation to be detected? Does it also encompass when methylation is not detected on the selected CpG site? In addition, the claim and the specification does not define what “on the basis of the detected DNA methylation” encompasses and it is unclear whether the status of a single position on a chromosome will be able to detect “whether a cell or tissue has upper urinary tract carcinoma”.
Regarding claim 12, the recitation of “pyrosequencing method, mass spectrometry” in line 2 of the claim followed by the recitation of “a bead array method or ion exchange chromatography” in lines 2-3 of the claim is unclear. It is unclear if a bead array and ion exchange chromatography are part of the same method performed for detection of the DNA methylation level, or if it is the result of a typographical error and should read “pyrosequencing method, mass spectrometry, a bead array method, or ion exchange chromatography”.
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 & 10-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites a method for identifying upper urinary tract urothelial carcinoma in a cell/tissue or subject through detecting a DNA methylation level of at least one CpG site selected from a group and then determining whether the cell/tissue or subject has upper urinary tract urothelial carcinoma on the basis of the detect DNA methylation level. This recitation is a natural correlation between DNA methylation level of at least on CpG site and whether the cell/tissue or subject has upper urinary tract urothelial carcinoma. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites identifying upper urinary tract urothelial carcinoma in a cell/tissue or subject and determining whether the subject has upper urinary urothelial carcinoma which are recitations of abstract ideas because it encompasses conclusions and determinations which can occur entirely within the mind. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of detecting DNA methylation level of at least one CpG site selected from a group in genomic DNA and treating the genomic DNA with bisulfite, however this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
The steps of detecting a DNA methylation level of at least one CpG site in genomic DNA are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
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.
Claim(s) 1, 3, 10, & 13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fujimoto (Fujimoto et al.; Vol. 108, page 1, April 15th, 2019), as cited in the IDS dated 06/27/2022.
Regarding claim 1, the specification, on pg. 47, teaches that the DNA methylation status of the instant application was analyzed using the Infinium Human Methylation 450K BeadChip assay that covers 99% of RefSeq genes and 96% of CpG islands. Fujimoto teaches the genome-wide DNA methylation analysis of upper urinary tract urothelial carcinoma tissue (cell or tissue containing upper urinary urothelial cell) and bladder urothelial carcinoma tissue using the 450K Infinium array (pg. 1 only paragraph lines 1-18), in which the 450K array encompasses all positions listed in claim 1 of the instant application including position 111,813,690 on chromosome 1, and then diagnosing upper urinary tract urothelial carcinoma between control and upper urinary tract urothelial carcinoma with the DNA methylation level (determining whether the cell or tissue has upper urinary tract carcinoma on the basis of the detected DNA methylation level).
Regarding claim 4, Fujimoto teaches that the DNA methylation quantification in a urine specimen is expected to enable diagnosis of upper urinary tract urothelial carcinoma (DNA is derived from an upper urinary tract urothelial cell contained in urine).
Regarding claim 10, the specification, on pg. 47, teaches that the DNA methylation status of the instant application was analyzed using the Infinium Human Methylation 450K BeadChip assay that covers 99% of RefSeq genes and 96% of CpG islands. Fujimoto teaches the genome-wide DNA methylation analysis of upper urinary tract urothelial carcinoma tissue (cell or tissue containing upper urinary urothelial cell) and bladder urothelial carcinoma tissue using the 450K Infinium array (pg. 1 only paragraph lines 1-18), in which the 450K array encompasses all positions listed in claim 1 of the instant application including position 111,813,690 on chromosome 1, and then diagnosing upper urinary tract urothelial carcinoma between control and upper urinary tract urothelial carcinoma with the DNA methylation level (determining whether the subject has upper urinary tract carcinoma on the basis of the detected DNA methylation level).
Regarding claim 13, Fujimoto teaches that the DNA methylation quantification in a urine specimen is expected to enable diagnosis of upper urinary tract urothelial carcinoma (DNA is derived from an upper urinary tract urothelial cell contained in urine).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2, 3, 11, & 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fujimoto (Fujimoto et al.; Vol. 108, page 1, April 15th, 2019), as cited in the IDS dated 06/27/2022, in view of Kitchen (Kitchen et al.; Epigenetics, Vol. 11, pages 237-246, April 2016).
The teachings of Fujimoto with respect to claims 1 & 10 are discussed above and incorporated herein.
Regarding claims 2 & 3, Fujimoto does not teach the detection of the DNA methylation level comprises treating the DNA with bisulfite (see claim 2) or the method performed to detect the DNA methylation level (see claim 3).
Kitchen teaches the genomic DNA was extracted and then bisulfite converted (genomic DNA treated with bisulfite) to quantify the DNA methylation at approximately 480,000 CpG sites across the genome (detecting the methylation level of at least one CpG site) using the Infinium-based Human Methylation450 (450K) BeadChip array (pg. 243 column 1 2nd full paragraph lines 1-10; pg. 243 paragraph bridging column 1 & 2 lines 1-6) (see claim 2). Kitchen also teaches the DNA methylation level was quantified through the Infinium-based HumanMethylation450 (450K) BeadChip Arrays (performed using a bead array method) (pg. 243 paragraph bridging column 1 & 2 lines 1-6) and further validated with pyrosequencing (pg. 243-244 paragraph bridging pg. 243 & pg. 244 lines 1-6) (see claim 3). Finally, Kitchen teaches that the use of the genome-wide DNA methylation analysis of the bladder cancer samples provide targets that can be used for novel therapeutics (pg. 242-243 paragraph bridging pg. 242 & pg. 243 lines 1-16).
Fujimoto and Kitchen are considered to be analogous to the claimed invention because they are all in the same field of detection of DNA methylation with the Human Methylation 450K BeadChip array in cancer samples. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting DNA methylation levels in upper urinary tract urothelial carcinoma tissue samples with the Infinium 450K array in Fujimoto to incorporate the detection of DNA methylation levels by treating the genomic DNA with bisulfite and detecting with a bead array method and pyrosequencing as taught in Kitchen because Kitchen teaches that doing so would provide a genome-wide method for the analysis of cancer samples to provide targets that can be used for novel therapeutics.
Regarding claims 11 & 12, Fujimoto does not teach the detection of the DNA methylation level comprises treating the DNA with bisulfite (see claim 11) or the method performed to detect the DNA methylation level (see claim 12).
Kitchen teaches the genomic DNA was extracted and then bisulfite converted (genomic DNA treated with bisulfite) to quantify the DNA methylation at approximately 480,000 CpG sites across the genome (detecting the methylation level of at least one CpG site) using the Infinium-based Human Methylation450 (450K) BeadChip array (pg. 243 column 1 2nd full paragraph lines 1-10; pg. 243 paragraph bridging column 1 & 2 lines 1-6) (see claim 11). Kitchen also teaches the DNA methylation level was quantified through the Infinium-based HumanMethylation450 (450K) BeadChip Arrays (performed using a bead array method) (pg. 243 paragraph bridging column 1 & 2 lines 1-6) and further validated with pyrosequencing (pg. 243-244 paragraph bridging pg. 243 & pg. 244 lines 1-6) (see claim 12). Finally, Kitchen teaches that the use of the genome-wide DNA methylation analysis of the bladder cancer samples provide targets that can be used for novel therapeutics (pg. 242-243 paragraph bridging pg. 242 & pg. 243 lines 1-16).
Fujimoto and Kitchen are considered to be analogous to the claimed invention because they are all in the same field of detection of DNA methylation with the Human Methylation 450K BeadChip array in cancer samples. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting DNA methylation levels in upper urinary tract urothelial carcinoma tissue samples with the Infinium 450K array in Fujimoto to incorporate the detection of DNA methylation levels by treating the genomic DNA with bisulfite and detecting with a bead array method and pyrosequencing as taught in Kitchen because Kitchen teaches that doing so would provide a genome-wide method for the analysis of cancer samples to provide targets that can be used for novel therapeutics.
Claim(s) 1-4 & 10-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kitchen (Kitchen et al.; Epigenetics, Vol. 11, pages 237-246, April 2016), in view of Guo (Guo et al.; Urologic Oncology, Vol. 36, pages e15-e23, April 2018), as cited on the IDS dated 07/22/2024.
Regarding claim 1, the specification, on pg. 47, teaches that the DNA methylation status of the instant application was analyzed using the Infinium Human Methylation 450K BeadChip assay that covers 99% of RefSeq genes and 96% of CpG islands. Kitchen teaches a genome-wide methylation analysis of genomic DNA in high-grade non-muscle invasive bladder cancer using the HumanMethylation450 (450k) BeadChip array, in which the 450K array encompasses all positions listed in claim 1 of the instant application including position 111,813,690 on chromosome 1, in bladder cancer tumors (tissue or cell containing carcinoma) compared to normal bladder controls (abstract lines 1-19; pg. 243 column 1 2nd full paragraph lines 1-10; pg. 243 paragraph bridging column 1 & 2 lines 1-6) for determining DNA methylation level in the development and progression of tumor types in bladder cancer (determining whether the cell or tissue has carcinoma on the basis of the detected DNA methylation level) (pg. 242-243 paragraph bridging pg. 242 & pg. 243 lines 1-10).
Kitchen does not teach the detection of genome-wide methylation analysis using the HumanMethylation450 BeadChip in upper urinary tract urothelial carcinoma.
Guo teaches a method for examining the methylation status in upper tract urothelial carcinoma (UTUC) in DNA samples extracted from cell fragments in urine sample obtained from patients with urothelial carcinoma (pg. e16 paragraph bridging column 1 & 2 lines 1-8; pg. e16 column 2 1st full paragraph lines 1-8). Guo also teaches that due to clinical and genomic similarities in bladder cancer and UTUC that the same panel of DNA methylation biomarkers in urine sediments could be useful for noninvasive and early detection in urothelial carcinoma (abstract methods paragraph lines 1-2; abstract results paragraph lines 1-6; pg. e16 column 1 1st full paragraph lines 1-20). Guo also teaches that urine DNA methylation markers (DNA methylation level) are a reliable, noninvasive, and cost-effective diagnostic tool for bladder carcinoma and UTUC (abstract conclusions paragraph lines 1-2).
Kitchen and Guo are considered to be analogous to the claimed invention because they are all in the same field of detection of DNA methylation levels in carcinoma. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting DNA methylation levels in bladder cancer samples using the 450K array in Kitchen to incorporate the detection of DNA methylation levels with this method in upper tract urothelial carcinoma (UTUC) as taught in Guo because Guo teaches that bladder and UTUC share clinical and genomic similarities and that the same panel of DNA methylation biomarkers in urine sediments can be useful for noninvasive and early detection in urothelial carcinoma (UTUC).
Regarding claim 2, Kitchen teaches the genomic DNA was extracted and then bisulfite converted (genomic DNA treated with bisulfite) to quantify the DNA methylation at approximately 480,000 CpG sites across the genome (detecting the methylation level of at least one CpG site) (pg. 243 column 1 2nd full paragraph lines 1-10; pg. 243 paragraph bridging column 1 & 2 lines 1-6).
Regarding claim 3, Kitchen teaches the DNA methylation level was quantified through the Infinium-based HumanMethylation450 (450K) BeadChip Arrays (performed using a bead array method) (pg. 243 paragraph bridging column 1 & 2 lines 1-6) and further validated with pyrosequencing (pg. 243-244 paragraph bridging pg. 243 & pg. 244 lines 1-6).
Regarding claim 4, Guo teaches a method for examining the methylation status in upper tract urothelial carcinoma (UTUC) in DNA samples extracted from cell fragments in urine sample obtained from patients with urothelial carcinoma (pg. e16 paragraph bridging column 1 & 2 lines 1-8; pg. e16 column 2 1st full paragraph lines 1-8).
Regarding claim 10, the specification, on pg. 47, teaches that the DNA methylation status of the instant application was analyzed using the Infinium Human Methylation 450K BeadChip assay that covers 99% of RefSeq genes and 96% of CpG islands. Kitchen teaches a genome-wide methylation analysis of genomic DNA in high-grade non-muscle invasive bladder cancer using the HumanMethylation450 (450k) BeadChip array, in which the 450K array encompasses all positions listed in claim 1 of the instant application including position 111,813,690 on chromosome 1, in bladder cancer tumors (tissue or cell containing carcinoma) compared to normal bladder controls (abstract lines 1-19; pg. 243 column 1 2nd full paragraph lines 1-10; pg. 243 paragraph bridging column 1 & 2 lines 1-6) for determining DNA methylation level in the development and progression of tumor types in bladder cancer (determining whether the subject has carcinoma on the basis of the detected DNA methylation level) (pg. 242-243 paragraph bridging pg. 242 & pg. 243 lines 1-10).
Kitchen does not teach the detection of genome-wide methylation analysis using the HumanMethylation450 BeadChip in upper urinary tract urothelial carcinoma.
Guo teaches a method for examining the methylation status in upper tract urothelial carcinoma (UTUC) in DNA samples extracted from cell fragments in urine sample obtained from patients with urothelial carcinoma (pg. e16 paragraph bridging column 1 & 2 lines 1-8; pg. e16 column 2 1st full paragraph lines 1-8). Guo also teaches that due to clinical and genomic similarities in bladder cancer and UTUC that the same panel of DNA methylation biomarkers in urine sediments could be useful for noninvasive and early detection in urothelial carcinoma (abstract methods paragraph lines 1-2; abstract results paragraph lines 1-6; pg. e16 column 1 1st full paragraph lines 1-20). Guo also teaches that urine DNA methylation markers (DNA methylation level) are a reliable, noninvasive, and cost-effective diagnostic tool for bladder carcinoma and UTUC (abstract conclusions paragraph lines 1-2).
Kitchen and Guo are considered to be analogous to the claimed invention because they are all in the same field of detection of DNA methylation levels in carcinoma. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting DNA methylation levels in bladder cancer samples using the 450K array in Kitchen to incorporate the detection of DNA methylation levels with this method in upper tract urothelial carcinoma (UTUC) as taught in Guo because Guo teaches that bladder and UTUC share clinical and genomic similarities and that the same panel of DNA methylation biomarkers in urine sediments can be useful for noninvasive and early detection in urothelial carcinoma (UTUC).
Regarding claim 11, Kitchen teaches the genomic DNA was extracted and then bisulfite converted (genomic DNA treated with bisulfite) to quantify the DNA methylation at approximately 480,000 CpG sites across the genome (detecting the methylation level of at least one CpG site) (pg. 243 column 1 2nd full paragraph lines 1-10; pg. 243 paragraph bridging column 1 & 2 lines 1-6).
Regarding claim 12, Kitchen teaches the DNA methylation level was quantified through the Infinium-based HumanMethylation450 (450K) BeadChip Arrays (performed using a bead array method) (pg. 243 paragraph bridging column 1 & 2 lines 1-6) and further validated with pyrosequencing (pg. 243-244 paragraph bridging pg. 243 & pg. 244 lines 1-6).
Regarding claim 13, Guo teaches a method for examining the methylation status in upper tract urothelial carcinoma (UTUC) in DNA samples extracted from cell fragments in urine sample obtained from patients with urothelial carcinoma (pg. e16 paragraph bridging column 1 & 2 lines 1-8; pg. e16 column 2 1st full paragraph lines 1-8).
Conclusion
Claims 1-4 & 10-13 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682