DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed May 18, 2026. Currently, claims 14, 16-22 are pending.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow.
Any objections and rejections not reiterated below are hereby withdrawn.
The 103 rejection has been withdrawn in view of the arguments the references do not teach using B3GALT6 as a reference.
Priority
This application claims priority to
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Drawings
The drawings are acceptable.
Information Disclosure Statement
It is noted that the IDS filed June 9, 2022, December 19, 2022, December 20, 2022, March 28, 2025, July 21, 2025 and December 19, 2025 contain an extremely large number of references for consideration by the Examiner. If the Applicant and/or Applicant and/or Applicant's representative are aware of any particular reference or portion of a reference in the extensive list which the examiner should pay particular attention to, it is required that it be specifically pointed out in response to this Office action.
Applicant is reminded that "burying" relevant references in a lengthy IDS is discouraged. See, e.g., Molins PLC v. Textron Inc., 48 F.3d 1172, 33 USPQ2d 1823, 1831 (Fed. Cir. 1995) The court concluded that, by “burying” Wagenseil in a multitude of other references, Hirsh and Smith intentionally withheld it from the PTO becausethis manner of disclosure was tantamount to a failure to disclose. Citing Penn Yan Boats, Inc. v. Sea Lark Boats, Inc., 359 F.Supp. 948, 175 USPQ 260 (S.D. Fla. 1972), aff'd, 479 F.2d 1328, 178 USPQ 577 (5th Cir.), cert. denied, 414 U.S. 874 (1973), the court stated that Hirsh's and Smith's failure to highlight Wagenseil in light of their knowledge of Whitson's actions in the foreign prosecutions violated their duty of candor to the PTO. Citing our precedent, Textron asserts that Smith's and Hirsh's conduct is “inexcusable, fraudulent, and cannot operate to cure Whitson's inequitable conduct.” See Rohm & Haas Co. v. Crystal Chem. Co., 722 F.2d 1556, 220 USPQ 289(Fed.Cir. 1983), cert. denied, 469 U.S. 851 (1984) (where intentional material misrepresentations have been made, a “cure” through voluntary efforts during prosecution must be demonstrated by clear, unequivocal, and convincing evidence).
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 14, 16-22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
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, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claim 14 is directed to preparing DNA, treating DNA and amplifying four or more methylated biomarkers, assaying B3GALT6 bisulfite treated DNA “calculating a normalized amount of the four methylated biomarkers using the amount of B3GALT6”.
Claim 14 is directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract step of “calculating a normalized” amount of the four methylated biomarkers to the amount of B3GALT6).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Claim 14 recites a mathematical calculation. The “calculating a normalized amount of each of the 4 methylated biomarker genes using the amount of the reference marker B3GALT6 is a mathematical calculation. This calculation is often a ratio or a simple subtraction formula to calculate normalized amounts.
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites obtaining a sample and bisulfite treating and amplifying, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The methylation status is a mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the methylation biomarkers of a sample without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the methylation through whatever known processes they wish to use.
The step of determining the methylation was well known in the art at the time the invention was made. The prior art teaches routinely performing methylation PCR for the claimed genes (see Ahlquist, for example). The steps are recited at a high level of generality. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Additionally, the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements were well known.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments
The response traverses the rejection. The response asserts the claim no longer recites a step of comparing. This argument has been considered but is not convincing because the claim has been amended to replace the comparing step with a mathematical calculation. The “calculating a normalized” amount is a mathematical formulation that often involves a simple subtraction step. The specification does not define “calculating a normalized” amount but the state of the art provides this involves a subtraction step.
The response further argues that the additional limitations are more than well-understood, routine and convention in the field. This argument has been reviewed but is not convincing. The analysis of bisulfite treated DNA and reference markers was well-understood, routine and conventional at the time the invention was made as exemplified by the art of record. As noted above, the courts have found that amplifying and sequencing genes were well understood, routine and conventional.
Thus for the reasons above and those already of record, the rejection is maintained.
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.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim(s) 14, 16-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist et al. (US 10,435,755, October 8, 2019) in view of Lewin et al. (WO2017129716, August 2017) and further in view of Allawi et al. (US 2018/0245157, August 30, 2018).
Claim(s) 14, 16-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist et al. (WO2016/160454, October 6, 2016) in view of Lewin et al. (WO2017129716, August 2017) and further in view of Allawi et al. (US 2018/0245157, August 30, 2018).
Ahlquist ‘755 and Ahlquist ‘454 teaches a method of characterizing an esophageal cell sample by preparing DNA from an ingestible sampling device. Ahlquist teaches non-endoscopic screening methods include swallowing a sponge on string device (Example 1 and V). DNA was extracted and bisulfite treated. Methylation of target genes was assayed by methylation-specific PCR or quantitative allele specific real-time target and signal amplification (Example 1, col. 44 and V, col. 60). Markers were normalized to b-actin and ZDHHC1. The methylation markers included NDRG4, VAV3 and ZNF682 (see Table 8). Table 8 further includes BMP3 and OPLAH.
Ahlquist ‘755 and Ahlquist ‘454 do not teach using analyzing SETP9 for characterizing esophageal cancer or using B3GALT6 as a reference gene in the methylation analysis.
However, Lewin teaches ANKRD13B is a hypermethylated CpG methylation biomarker for esophageal squamous cell carcinoma patients (Figure 3). Lewin teaches Figure 3B illustrates the methylation degree of ANKRD13B in DNA from esophagus cancer and illustrates it is more than 10% in contract to normal tissue.
Further, Allawi et al teaches the use of B3GALT6 as a gene for use in normalizing nucleic acid detection assays (para 107). Allawi teaches using reference genes such as B3GALT6 in diagnostic assay for identifying methylation associated with cancers (para 182).
Therefore, it would have been prima facie obvious at the time the invention was made to have modified the methylation detection methods of Ahlquist ‘755 or Ahlquist ‘454 to include detecting SEPT9, another esophageal methylation marker. Lewin teaches ANKRD13B is a hypermethylated CpG methylation biomarker for esophageal squamous cell carcinoma patients (Figure 3). It would have been obvious to choose from the finite number of identified, predictable solutions, with a reasonable expectation of success (see MPEP 2143(e)). Here, the art teaches methylation DNA markers including at least NDRG4, VAV3 and ZNF682, BMP3, OPLAH and ANKRD13B are all esophageal methylation markers. This is a situation of obvious to try. The diagnosis of esophageal cancers was an art recognized problem that many skilled artisans were studying, including studying methylation profiles of NDRG4, VAV3 and ZNF682, BMP3, OPLAH and ANKRD13B. Thus, there was an art recognized problem. The art teaches a finite number of markers. It would have been obvious to select the genes that were found to be methylated in the same cancer. Applicant does not identify a secondary consideration demonstrating criticality or anything unexpected about the combination of known prior art methylation markers. Thus, methylation analysis of these genes using two sets of primer pairs would have been prima facie obvious.
Further, Ahlquist teaches using a reference gene sequence but does not teach B3GALT6. The ordinary artisan would have been motivated to have used B3GALT6, a known methylation reference gene.
Response to Arguments
The response traverses the rejection. The response asserts the newly amended claims fail to disclose or suggest amplifying bisulfite treated DNA from an esophageal cell using an ingestible sampling device to measure 4 or more biomarkers and B3GALT6 reference marker to calculate normalized amount of biomarkers. The response states all of the references are silent on B3GALT6. This argument has been considered but is not convincing. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Allawi teaches measuring B3GALT6 as a reference marker. Allawi specifically teaches that genes that find uses normalizing nucleic acid detection assay on human samples includes b-actin, ZDHHC1 and B3GALT6. Allawi teaches these genes are substitutable one for another. The ordinary artisan would have had a reasonable expectation of success to measure B3GALT6 from esophageal cell samples and used B3GALT6 to calculated normalized amount of biomarkers. In fact, the list of genes taught in Allawi are overlapping with the instant claims. Thus, using B3GALT6 with the same genes to normalize methylation markers would have been prima facie obvious absent unexpected results.
The response states that none of the cited references disclose or suggest use of B3GALT6 reference in esophageal cells collected from an ingestible device. This argument has been reviewed but is not persuasive. As discussed above, Allawi teaches B3GALT6 is a reference gene used to normalize nucleic acid and is taught as an equivalent for this purpose with b-actin and ZDHHC1. The ordinary artisan would have had a reasonable expectation that substituting B3GALT6 for the other known reference genes would have produced predictable results. The response has not demonstrated any unpredictability of using an equivalent reference gene for normalizing methylation biomarkers. Thus for the reasons above and those already of record, the rejection is maintained.
Claim(s) 14, 16-19, 21-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Markowitz et al. (US 2022/0243281, provisional May 28, 2019) in view of Allawi et al. (US 2018/0245157, August 30, 2018).
With respect to Claims 14 Markowitz teaches a method of diagnosing a subject as having a neoplasia (e.g., esophageal cancer) by determining whether a target gene in a sample from the subject is more methylated than a reference target gene (page 57, lines 11-15). Markowitz teaches neoplasia refers to Barrett’s esophagus and esophageal cancer (page 17, lines 22-25). Markowitz teaches methods for assaying DNA methylation of NDRG4, VAV3, ZNF682 and DOCK2 (see para 4, col. 2, lines 1-5). Markowitz teaches the esophageal sample may be collected using a swallowable balloon for collecting samples (para 139).
With respect to Claim 16, 17, 18, Markowitz also teaches analysis of BMP3, ZNF568 and FER1L4 (see Table 1, pages 12-13).
With respect to Claim 20, Markowitz teaches numerous methods for detecting methylation such as MSP, MS-SnuPE, COBRA that rely upon primers and amplification, for example (pages 50-52).
With respect to Claims 21-22, Markowitz teaches the sample may be obtained by brushing of the esophagus with a brush, cytology brush, sponge, balloon or substance that contacts the esophagus and obtains and esophageal sample (page 17, lines 27-30).
Markowitz does not teach using B3GALT6 as a reference gene in the methylation analysis.
However, Allawi et al teaches the use of B3GALT6 as a gene for use in normalizing nucleic acid detection assays (para 107). Allawi teaches using reference genes such as B3GALT6 in diagnostic assay for identifying methylation associated with cancers (para 182).
Therefore, it would have been prima facie obvious at the time the invention was made to have modified the methylation detection methods of Markowitz to include the B3GALT6 reference gene. Markowitz teaches using a reference gene sequence but does not teach B3GALT6. The ordinary artisan would have been motivated to have used B3GALT6, a known methylation reference gene.
Response to Arguments
The response traverses the rejection. The response asserts Markowitz is directed to storage solutions for preserving DNA methylation patterns. This argument has been reviewed but is not persuasive. The instant claims merely require the claims are a method. Further Markowitz teaches a method of diagnosing a subject as having a neoplasia (e.g., esophageal cancer) by determining whether a target gene in a sample from the subject is more methylated than a reference target gene (page 57, lines 11-15). Markowitz teaches neoplasia refers to Barrett’s esophagus and esophageal cancer (page 17, lines 22-25). Markowitz teaches methods for assaying DNA methylation of NDRG4, VAV3, ZNF682 and DOCK2 (see para 4, col. 2, lines 1-5). Markowitz teaches the esophageal sample may be collected using a swallowable balloon for collecting samples (para 139). Thus, the teachings of Markowitz are not limited to preserving DNA methylation patterns. A reference may be used for all that it teaches and is not limited to preferred embodiments.
The response argues Markowitz fails to disclose or suggest B3GALT6 as a reference maker. As discussed above, this argument has been considered but is not convincing. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Allawi teaches measuring B3GALT6 as a reference marker. Allawi specifically teaches that genes that find uses normalizing nucleic acid detection assay on human samples includes b-actin, ZDHHC1 and B3GALT6. Allawi teaches these genes are substitutable one for another. The ordinary artisan would have had a reasonable expectation of success to measure B3GALT6 from esophageal cell samples and used B3GALT6 to calculated normalized amount of biomarkers. In fact, the list of genes taught in Allawi are overlapping with the instant claims. Thus, using B3GALT6 with the same genes to normalize methylation markers would have been prima facie obvious absent unexpected results.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 14, 16, 18-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,319,969 in view of Lewin et al. (WO2017129716, August 2017) and further in view of Allawi et al. (US 2018/0245157, August 30, 2018) and Lao-Sirieix et al. (Gut, "Non-endoscopic immunocytological screening test for Barrett's oesophagus, June 12, 2007).
Although the conflicting claims are not identical, they are not patentable distinct from each other because Claims 14, 16-22 of the instant application is generic to all that is recited in claims 1-14 of U.S. Patent No. 12,319,969. That is, claims 1-14 of U.S. Patent No. 12,319,969 falls entirely within the scope of Claims 14, 16-22, or in other words, Claims 14, 16-22 are anticipated by claims 1-14 of U.S. Patent No. 12,319,969. Here, claims 1-14 of U.S. Patent No. 12,319,969 recites “extracting genomic DNA from a human suspected of having or having an esophageal disorder, treating the extracted DNA with bisulfite, amplifying the methylation level” and assaying at least one biomarkers comprising VAV3. Claim 2 of ‘969 further requires NDRG4 and, ZNF682. Claim 14 further recites BMP3, FER1L4, and ZNF568”. The combination in the instant claims encompasses additional genes, including the combination of genes claimed in ‘969.
The claims of ‘969 do not teach analysis of ANKRD13B, comparing the methylation to a reference marker, namely B3GALT6 or obtaining a sample using an ingestible sampling device.
However, Lewin teaches ANKRD13B is a hypermethylated CpG methylation biomarker for esophageal squamous cell carcinoma patients (Figure 3). Lewin teaches Figure 3B illustrates the methylation degree of ANKRD13B in DNA from esophagus cancer and illustrates it is more than 10% in contract to normal tissue.
Moreover, Allawi et al teaches the use of B3GALT6 as a gene for use in normalizing nucleic acid detection assays (para 107). Allawi teaches using reference genes such as B3GALT6 in diagnostic assay for identifying methylation associated with cancers (para 182).
Further, Lao-Sirieix teaches obtaining a sample of cells using a capsule sponge. The device consists of a sponge contained within a gelatin capsule that dissolved in the stomach within 5 minutes. The sponge is removed from the stomach up thru the esophagus.
Therefore, it would have been prima facie obvious at the time the invention was made to have modified the methylation detection methods of ‘969 to include analysis of the known esophageal methylation marker ANKRD13B and the B3GALT6 reference gene to compare methylation levels to a control. The ordinary artisan would have been motivated to have included known esophageal methylation markers and used B3GALT6, a known methylation reference gene. Further it would have been obvious to have used a capsule sponge to collect esophageal cells in a less invasive manner.
Response to Arguments
The response traverses the rejection. The response argues Allawi fails to disclose or suggest B3GALT6 as a reference maker in an esophageal cell sample. As discussed above, this argument has been considered but is not convincing. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Allawi teaches measuring B3GALT6 as a reference marker. Allawi specifically teaches that genes that find uses normalizing nucleic acid detection assay on human samples includes b-actin, ZDHHC1 and B3GALT6. Allawi teaches these genes are substitutable one for another. The ordinary artisan would have had a reasonable expectation of success to measure B3GALT6 from esophageal cell samples and used B3GALT6 to calculated normalized amount of biomarkers. In fact, the list of genes taught in Allawi are overlapping with the instant claims. Thus, using B3GALT6 with the same genes to normalize methylation markers would have been prima facie obvious absent unexpected results.
Claims 14, 16-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 16-17, 22 of copending Application No. 17/727,128 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘128 application claims a combination comprising the instantly claimed genes.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the conflicting claims are not identical, they are not patentable distinct from each other because Claims 14, 16-22 of the instant application is generic to all that is recited in claims 1-4, 6, 16-17, 22 of copending Application No. 17/727,128. That is, claims 1-4, 6, 16-17, 22 of copending Application No. 17/727,128 falls entirely within the scope of Claims 14, 16-22, or in other words, Claims 14, 16-22 are anticipated by claims 14, 16-18, 20 of copending Application No. 17/233,199. Here, claims 1-4, 6, 16-17, 22 of copending Application No. 17/727,128 recites “a method comprising treating DNA from an esophageal tissue sample, amplifying DNA using primers specific for FER1L4, ZNF568, BMP3, NDRG4, VAV3, and ZNF682 (see claim 6, element 1)
and measuring methylation level of B3GALT6 as a reference gene. The combination in the instant claims encompasses additional genes, including the combination of genes claimed in ‘128. Claim 22 of ‘128 is directed to a collection device having an absorbing member capable of collecting the esophageal tissue sample upon contact with a bodily region.
Response to Arguments
The Applicant requests that this rejection be held in abeyance until allowable subject matter is found in the pending application. This request has been noted and is denied. See 804(I)(b)(1) and 37 C.F.R. 1.111(b), which allows that some objections may be held in abeyance but includes no provision for holding rejections in abeyance. Thus, for the reasons above and those already of record, the rejection is maintained.
Claims 14, 16-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44-51 of copending Application No. 17/996,032 (reference application) in view of Allawi et al. (US 2018/0245157, August 30, 2018). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘032 application claims a combination comprising the instantly claimed genes.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the conflicting claims are not identical, they are not patentable distinct from each other because Claims 14, 16-22 of the instant application is generic to all that is recited in claims 44-51 of copending Application No. 17/996,032. That is, claims 44-51 of copending Application No. 17/996,032 falls entirely within the scope of Claims 14, 16-22, or in other words, Claims 14, 16-22 are anticipated by claims 44-51 of copending Application No. 17/996,032. Here, claims 44-51 of copending Application No. 17/996,032 recites “assaying at least one biomarkers comprising NDRG4, VAV3, ZNF682, FER1L4, BMP3 and ZNF568”. The combination in the instant claims encompasses additional genes, including the combination of genes claimed in ‘032.
The claims of ‘032 do not teach comparing the methylation to a reference marker, namely B3GALT6.
However, Allawi et al teaches the use of B3GALT6 as a gene for use in normalizing nucleic acid detection assays (para 107). Allawi teaches using reference genes such as B3GALT6 in diagnostic assay for identifying methylation associated with cancers (para 182).
Therefore, it would have been prima facie obvious at the time the invention was made to have modified the methylation detection methods of ‘032 to include the B3GALT6 reference gene to compare methylation levels to a control. The ordinary artisan would have been motivated to have used B3GALT6, a known methylation reference gene.
Response to Arguments
The Applicant requests that this rejection be held in abeyance until allowable subject matter is found in the pending application. This request has been noted and is denied. See 804(I)(b)(1) and 37 C.F.R. 1.111(b), which allows that some objections may be held in abeyance but includes no provision for holding rejections in abeyance. Thus, for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable.
Cited pertinent art:
Jammula et al. (Gastroenterology, Vol. 158, No. 6, pages 1682, 1697, May 2020). Jammula teaches identification of subtypes of Barretts Esophagus and Esophageal adenocarcinoma based on methylation profiles. Jammula uses the Illumina 450K which comprises probes for each of the claimed gene.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
May 26, 2026
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