DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Herein, “the previous Office action” refers to the Non-Final Rejection filed 2/27/2025.
Amendments Received and Election/Restrictions
Amendments to the claims were received on 7/24/2025. Applicant’s amendment of the claims (filed 7/24/2025) introduces new claim 19, which depends on (and incorporates all of the limitations of) claim 6.
Claim 6 stands withdrawn pursuant to 37 CFR 1.142(b) as being directed to a nonelected invention, there being no currently allowable generic or linking claim. Election without traverse was made in the reply filed 1/14/2025. Accordingly, claim 19 is hereby withdrawn pursuant to 37 CFR 1.142(b) as being directed to a nonelected invention.
Priority
As detailed on the Filing Receipt filed 3/31/2021, the instant application claims priority to as early as 5/31/2018. At this point in prosecution, all claims are accorded the earliest claimed priority date.
Claim Status
Claims 7-8, 10-12 and 14-15 are canceled.
Claims 1-6, 9, 13 and 16-19 are pending.
Claims 6 and 19 stand withdrawn, as detailed above.
Claims 1-5, 9, 13 and 16-18 are under examination.
Withdrawn Objections/Rejections
The objection to the specification is hereby withdrawn in view of Applicant’s amendment of the specification to remove browser-executable code.
The rejection of claims 1-5, 9-13 and 15-18 under 35 USC § 112(b), as being indefinite, is hereby withdrawn in view of Applicant’s amendment of claims 1 and 4 to remove reference to external tables, cancelation of claims 10-12 and 15, and persuasive argument that the metes and bounds of claim 18 are sufficiently clear (remarks filed 7/24/2025 at pg. 13, para. 5 – pg. 14, para. 1).
The rejection of claims 10-12 and 15 under 35 USC § 101, as being directed to nonstatutory subject matter, is hereby withdrawn in view of Applicant’s cancelation of the claims.
The rejection of claims 1-5, 9-10 and 15-17 under 35 USC § 102, as being anticipated by Adams (WO 2015/124921), as evidenced by Chang (WO 2013/082288), is hereby withdrawn in view of Applicant’s amendment of claim 1 and cancelation of claims 10 and 15.
The rejection of claims 11-12 under 35 USC § 103, as being unpatentable over Adams, in view of Chang, is hereby withdrawn in view of Applicant’s cancelation of the claims.
Claim Objections
Claim 1 is objected to because of the following informalities:
With respect to claim 1, the recited “a percentage of CpG sites of (a) that are methylated exceeds 40% is indicative of IBS” (lines 17-18) should be amended to, e.g., “a percentage that exceeds 40% is indicative of IBS” for improved grammatical clarity. Prior recitation of “the percentage of CpG sites… that are methylated” (lines 16-17) provides sufficient antecedent basis such that the identity of the referenced percentage is clear.
Appropriate correction is required.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using
the plain meaning of the claim language in light of the specification as it would be understood
by one of ordinary skill in the art. This section documents the Examiner’s interpretation of
certain claim elements under this standard.
“The broadest reasonable interpretation of a method (or process) claim having
contingent limitations requires only those steps that must be performed and does not include
steps that are not required to be performed because the condition(s) precedent are not met”
(MPEP 2111.04 § II).
Claim 1 recites the limitation of “administering rifamaxin… and/or a neuromodulator when the percentage of CpG sites methylated exceeds 40%” (lines 19-21).
This limitation only requires performance of an active step (“administering”) when a condition precedent is met, and is therefore considered as a contingent limitation. For purposes of prosecution, contingent limitations are not included in the broadest reasonable interpretation of the claims (MPEP 2111.04 § II).
Response to Arguments - Claim Rejections Under 35 USC § 101
In the remarks filed 7/24/2025, Applicant traverses the rejection under 35 USC § 101 and notes that the filed amendment of the claims more clearly incorporates the treatment step in operative connection to prior method steps (pg. 14, para. 3). The Examiner agrees that the amended treatment step of claim 1 exhibits operative connection to prior method steps. However, the amended step is in contingent form, and therefore not considered to fall within the broadest reasonable interpretation of the claims (see ‘Claim Interpretation’ section).
Thus, the argument is found unpersuasive and the rejection is maintained. The Examiner suggests amendment to render said step non-contingent. Were said step required under the broadest reasonable interpretation of the claims, it would likely be considered to apply the recited judicial exceptions to effect a particular treatment for a medical condition (as detailed in MPEP 2106.04(d)(2)).
Claim Rejections - 35 USC § 101
35 USC § 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 1-5, 9, 13 and 16-18 are rejected under 35 USC § 101 because the claimed invention is directed to non-statutory subject matter. This rejection is maintained from the previous Office action, and has been revised to address the amended claims (filed 7/24/2025).
"Claims directed to nothing more than abstract ideas, natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts (including formulas, equations and calculations), and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). Laws of nature and natural phenomena include principles, relations, and products that are naturally occurring or do not have markedly different characteristics compared to what occurs in nature (MPEP 2106.04(b)). The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than an abstract idea and a natural phenomenon.
Step 1: The Four Categories of Statutory Subject Matter (MPEP 2106.03)
The claims are directed to a method, which falls under the ‘process’ category of statutory subject matter.
Step 2A, Prong One: Whether the Claims Set Forth or Describe a Judicial Exception (MPEP 2106.04 § II.A.1)
‘Mathematical concepts’ are relationships between variables and numbers, numerical formulas or equations, or acts of calculation, which need not be expressed in mathematical symbols (MPEP 2106.04(a)(2) § I). The claims recite elements which encompass mathematical concepts, at least under their broadest reasonable interpretation, including:
“calculating the percentage of CpG sites on the IBS/IBD biomarker genes that are methylated, wherein a percentage of CpG sites methylated in excess of 40% is indicative of IBS or IBD” (claim 1), i.e., calculating a percentage, having particular significance, from measured values; and
“determin[ing] a conditional probability of IBS based on the profile” (claim 9), i.e., calculating a probability from measured values.
The recited acts of calculation constitute mathematical concepts.
‘Mental processes’ are processes that can be performed in the human mind at least with use of a physical aid, e.g., a slide rule or pen and paper (MPEP 2106.04(a)(2) § III). The recited acts of calculation are practicably performable in the human mind, rendering them as mental processes. Additionally, the claims recite additional elements that encompass further processes that are practicably performable in the human mind, at least under their broadest reasonable interpretation, including:
“the amount of biomarker methylation is used to classify the profile” (claim 1), i.e., labeling information based on measured values.
The recited steps of evaluating information, which are practicably performable in the human mind, constitute mental processes.
Hence, the claims recite elements that, individually and in combination, constitute an abstract idea.
Additionally, the claims recite steps of generating a genetic profile from a biological sample from a subject, measuring methylation of particular CpG sites on IBS/IBD biomarker genes in a biological sample, and classifying the profile (e.g., according to disease state) based on the measured data (claim 1). The claims further require that the biomarker genes are selected from particular genes that are differentially methylated between various disease states (claims 6-8 and 10), and require that the classification is based on methylation percentage as claimed (claims 11 and 14).
The claimed methods rely on natural correlations between expressed methylation patterns and inflammatory bowel disease states, i.e., laws of nature. See, e.g., Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F.3d 1117, 1135-36 (Fed. Cir. 2018). Hence, the claims recite elements that constitute a natural phenomenon.
The claims must therefore be examined further to determine whether they integrate these judicial exceptions into a practical application (MPEP 2106.04(d)).
Step 2A, Prong Two: Whether the Claims Contain Additional Elements that Integrate the Judicial Exception(s) into a Practical Application (MPEP 2106.04 § II.A.2)
The claims recite additional elements that gather data necessary for performance of claimed method steps, including:
“generating a… methylation profile from the biological sample obtained from [a] subject… compris[ing] at least [a recited list of] 50 CpG sites of IBS/IBD biomarker genes” (claim 1) wherein:
“generating the… profile comprises preprocessing the biological sample with a kit for measuring the amount of methylation on all CpG sites” (claim 5); and
“measuring the amount of methylation in the IBS/IBD biomarker genes” (claim 1).
Necessary data gathering is considered to be insignificant pre-solution activity, and as such insufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g)).
Further claim elements delimit embodiments of the above data gathering steps (but do not alter their characterization as such), including:
“the subject has manifested clinical symptoms associated with IBS” (claim 2);
“the subject has manifested clinical symptoms associated with IBD” (claim 3);
“the methylation profile comprises [recited] CpG sites” (claim 4);
“the biological sample comprises blood, plasma, serum, or mucosal tissue” (claim 16), wherein “the sample is peripheral blood mononuclear cells (PBMCs), peripheral blood lymphocytes, or whole blood” (claim 17); and
“the amount of biomarker methylation is greater than 54% of CpG sites on the IBS/IBD biomarker genes” (claim 18).
These elements limit the data gathering steps to gathering of data from particular sources (e.g., a sample from a subject manifesting symptoms of IBS) and data of particular representative significance (e.g., methylation levels of particular genes). The courts have ruled that such limitations merely confine judicial exceptions to particular fields of use (see Ultramercial, Inc. v. Hulu, LLC, 772 F.3d 709, 716 (Fed. Cir. 2014); Electric Power Group, LLC v. Alstom S.A., 830 F.3d 1350, 1354 (Fed. Cir. 2016)). Field-of-use limitations are insufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(h)).
The claims further recite the following additional elements that requires performance of a claimed function on a computer:
“a computer algorithm determines [the] conditional probability” (claim 9).
The claims do not describe any specific computational steps by which a computer performs or carries out this function, which is drawn to the recited abstract idea (as detailed above), nor do they provide any details of how specific structures of a computer are used to implement the function. The claims therein state nothing more than that a generic computer performs a function drawn to the abstract idea, and the element therefore amounts to mere instruction to apply the abstract idea using a computer. Mere instructions to apply judicial exceptions using a computer are insufficient to integrate judicial exceptions into a practical application (see MPEP 2106.04(d) § I and 2106.05(f)).
The claims further recite the following limitations that requires administration of treatment:
“administering rifamaxin… and/or a neuromodulator when the percentage of CpG sites methylated exceeds 40%” (claim 1), wherein “the treatment further comprises dietary therapy, or behavioral therapy” (claim 13); and
This limitation is currently recited in contingent form, and not considered to fall within the broadest reasonable interpretation of the claims (see ‘Claim Interpretation’ section).
Were said limitations required under the broadest reasonable interpretation of the claims (i.e., were it rendered non-contingent by appropriate amendment), they would likely be considered to comprise additional elements that apply the recited judicial exceptions to effect a particular treatment for a medical condition (as detailed in MPEP 2106.04(d)(2)).
No further additional elements are recited.
When the claims are considered as a whole: they do not improve the functioning of a computer, other technology, or technical field (MPEP 2106.04(d)(1) and 2106.05(a)); they do not apply the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition (MPEP 2106.04(d)(2)); they do not implement the judicial exceptions with, or in conjunction with, a particular machine (MPEP 2106.05(b)); they do not effect a transformation or reduction of a particular article to a different state or thing (MPEP 2106.05(c)); and they do not apply or use the judicial exceptions in some other meaningful way beyond linking the use of the judicial exceptions to particular technological environments and/or fields of use (e.g., treatment of IBS; MPEP 2106.05(e) and 2106.05(h)).
Therefore, the claims do not integrate the judicial exceptions into a practical application. See MPEP 2106.04(d) § I.
Because the claims recite an abstract idea and a natural phenomenon, and do not integrate those judicial exceptions into a practical application, the claims are directed to those judicial exceptions. Claims that are directed to judicial exceptions must be examined further to determine whether the additional elements besides the judicial exceptions render the claims significantly more than the judicial exceptions. Additional elements besides the judicial exceptions may constitute inventive concepts that are sufficient to render the claims significantly more (MPEP 2106.05).
Step 2B: Whether the Claims Contain Additional Elements that Amount to an Inventive Concept (MPEP 2106.05)
As noted above, several recited additional elements amount to insignificant extra-solution activity. Mere addition of insignificant extra-solution activity does not amount to an inventive concept that would render the claims significantly more than the recited judicial exceptions, particularly when the activities are well-understood or conventional (MPEP 2106.05(g)). The conventionality of recited additional elements that amount to insignificant extra-solution activity must be further considered.
Recited additional elements amounting to insignificant extra-solution activity encompass the following structures and processes, which are indicated as activity that may be performed with commercially-available products by the instant specification (see MPEP 2106.07(a) § III):
Generating a methylation profile, i.e., preprocessing a sample with a methylation kit, and measuring amounts of methylation:
“generating the IBS methylation profile comprises preprocessing the biological sample with a kit for measuring the amount of methylation on all CpG sites. Methylation can be measured using commercially available kits” (pg. 9, para. 0048);
“For global methylation profiling, we used the lllumina lnfinium HumanMethylation450 (HM450) BeadChip (lllumina, San Diego, CA), which interrogates DNA methylation status of > 450,000 CpGs and >99% of all genes. We performed bisulfite conversion on 1 μg of genomic DNA from each sample using the EZ-96 DNA Methylation Kit (Zymo Research, Irvine, CA) according to the manufacturer's instructions and as described previously and hybridized to HM450 BeadChips. These were subsequently scanned using the lllumina HiScanSQ system” (pg. 19, para. 0090).
Additionally, administration of recited species of treatment is indicated as well-understood, routine and conventional by relevant prior art. The cited article by Trinkley et al (J. Clin. Pharm. Ther. 36:275-282; published 2011) reviews IBS treatments and provides evidence for conventionality of the following treatments: rifaximin (pg. 278, l. column), loperamide (pg. 277, l. column); lubiprostone (pg. 278, r. column); fiber supplements, i.e., laxatives and dietary therapy (pg. 277, l. column); tricyclic antidepressants, i.e., antihistamine neuromodulators (pg. 276, r. column; pg. 277, r. column); and antispasmodics (pg. 278, l. column).
Hence, the encompassed pre- and post-solutional activity is considered well-understood, routine and conventional. Well-understood, routine and conventional activities are insufficient to constitute an inventive concept that would render the claims significantly more than judicial exceptions (MPEP 2106.05(d)).
Mere instructions to implement judicial exceptions using a computer are, when considered individually, similarly insufficient to constitute an inventive concept that would render the claims significantly more than said judicial exceptions (see MPEP 2106.05(f)).
Mere indications of field of use are similarly insufficient to constitute an inventive concept that would render the claims significantly more than judicial exceptions (MPEP 2106.05(h)).
When the claims are considered as a whole, they do not integrate the judicial exceptions into a practical application; they do not confine the use of the judicial exceptions to a particular technology; they do not solve a problem rooted in or arising from the use of a
particular technology; they do not improve a technology by allowing the technology to
perform a function that it previously was not capable of performing; and they do not
provide any limitations beyond generally linking the use of the judicial exceptions to particular technological environments and/or fields of use (e.g., treatment of IBS; MPEP 2106.05(e) and 2106.05(h)).
Therefore, the claims do not provide an inventive concept and/or significantly more than the judicial exceptions themselves. See MPEP 2106.05.
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole, are directed to judicial exceptions and lack an inventive concept. Hence, the claimed invention does not constitute significantly more than the judicial exceptions, so the claims are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Response to Arguments - Claim Rejections Under 35 USC §§ 102 and 103
In the remarks filed 7/24/2025, Applicant traverses the rejections under 35 USC §§ 102-3 and highlights alleged distinction between the claimed subject matter and the teachings of the applied art.
Applicant notes amendment of the claims to clarify direction to distinguishing between the conditions IBS and IBD, and alleges that Adams makes no mention of IBS and does not address the problem solved by the claimed invention (pg. 14, paras. 5-7).
Adams does in fact expressly mention differentiation of IBD subtypes and IBS. While discussing statistical analysis of gathered methylation data, Adams states that “multinomial logistic regression… may be used to classify into more groups, such as Crohn’s, Ulcerative colitis, irritable bowel syndrome & other disorders” (pg. 18, para. 1).
Thus, the presented argument of distinction is found unpersuasive. However, upon further review, Adams is not considered to teach the amended limitations of claim 1 pertaining to methylation percentages and administration of recited treatment(s). Hence, the rejection under § 102 has been withdrawn.
Applicant alleges that Adams does not mention detection or treatment of IBS (pg. 14, para. 8 – pg. 15, para. 1). As detailed above, Adams does in fact mention detection of IBS. Adams also discloses selecting a treatment other than an anti-IBD treatment, if the presence of IBD has not been identified (pg. 10, para. 4), but does not particularly disclose treatment of IBS. Adams is not applied under § 103 in isolation, but rather in combination with Chang.
Chang teaches administering a treatment to patients identified as expressing methylation patterns associated with IBS (pg. 20, para. 2). The presented argument of distinction is found unpersuasive, and the rejection is maintained.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 USC §§ 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.
The following is a quotation of 35 USC § 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.
The factual inquiries for establishing a background for determining obviousness under 35 USC § 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 USC § 102(b)(2)(C) for any potential 35 USC § 102(a)(2) prior art against the later invention.
Claims 1-5, 9, 13 and 16-18 are rejected under 35 USC § 103 as unpatentable over Adams et al (WO 2015/124921; effectively filed 2/19/2014; on IDS filed 3/1/2021), in view of Chang et al (WO 2013/082288; effectively filed 11/29/2011; on IDS filed 3/1/2021). The new grounds of rejection presented herein were necessitated by Applicant’s amendment of the claims (filed 7/24/2025).
Claim 1 is directed to a method of measuring DNA methylation in a subject sample, comprising steps of: generating a biomarker gene profile from the sample and measuring the amount of methylation in the biomarker genes, wherein the amount of methylation is used to classify the profile.
The claim further requires that the profile comprise at least 50 CpG sites of particular irritable bowel syndrome/inflammatory bowel disease (IBS/IBD) biomarker genes.
With respect to claim 1, Adams discloses methods for determining the presence of inflammatory bowel disease (Abstract), comprising steps of: providing a sample from an individual (pg. 2, para. 5); determining methylation state at 50 or more CpG sites (pg. 15, para. 5); and analyzing the measured data to classify the individual (pg. 17, para. – pg. 18, para. 1). Adams characterizes the disclosed methodology as assessment of methylation profiles (pg. 95, para. 1; pg. 113, para. 1). Adams further discloses use of an Illumina 450k methylation microarray to measure methylation levels, and cites a link to Web content therein (pg. 32, para. 4). Review with the Wayback Machine confirms that, at the time of Adams’ earliest priority filing (2/19/2014), the cited link led to a product information page for the ‘Infinium Human Methylation 450 BeadChip array’ sold by Illumina.
The instant specification states: “The Tables herein, such as Tables 16-20, provide annotations of CpG islands connected with a ‘cg number’. This information is provided by Illumina and can be used to identify the context of the sequences and probes to be used in the methods and assays described herein” (pp. 8-9, para. 0044). The specification then provides links to a manifest file with additional information, which upon review was found to list all markers assessed by the Infinium Human Methylation 450K BeadChip microarray product (including those recited in the claim). In this way, the instant specification indicates that utilizing the microarray product exemplified by Adams comprises analysis of the recited CpG sites (e.g., cg19067791).
Adams also discloses analyzing whether one or more of the CpG sites being tested exhibit a lower or greater level of methylation than those of a control (pg. 17, para. 6), but does not disclose calculating the percentage of CpG sites that are methylated, wherein a percentage in excess of 40% is indicative of IBS.
Adams additionally discloses treating an evaluated individual with a selected treatment, and exemplifies various anti-IBD treatments that may be selected for an individual identified as having IBD (pg. 10, para. 4). Adams further discloses selecting a treatment other than an anti-IBD treatment if the presence of IBD has not been identified (pg. 10, para. 4). However, Adams does not disclose administering the recited treatments when the percentage of CpG sites methylated exceeds 40%.
Chang discusses methods of detecting and analyzing patterns of methylation associated with irritable bowel syndrome (pg. 1, para. 3; pg. 3, paras. 2-3), comprising steps of: obtaining a sample of peripheral blood lymphocytes (pg. 3, para. 3); performing bisulfite conversion using a kit for detecting methylation status (pg. 23, para. 3); measuring methylation of CpG sites (pg. 27, para. 1); and classifying each sample based on the methylation (pg. 124, paras. 4-6).
Chang teaches analysis of methylation patterns that are specific for IBS, to differentially diagnose a patient having symptoms that are common to IBS and IBD (pg. 19, para. 2). In particular, Chang teaches calculating the percentage of methylation at tested CpG sites wherein at least 60 or 70% methylation (i.e., a percentage of methylation that exceeds 40%) at tested CpG sites provides evidence of irritable bowel syndrome (pg. 17, para. 3).
Chang also teaches administering a treatment to patients identified as expressing methylation patterns associated with IBS, and exemplifies various therapeutic agents including: loperamide, alosetron, lubiprostone, linaclotide, laxatives, and tricyclic antidepressants, i.e., antihistamine neuromodulators. Chang discusses the action of certain agents against particular symptoms of IBS, e.g., loperamide for diarrhea and lubiprostone for constipation (pg. 20, para. 2 - pg. 21, para. 1).
With respect to claims 2-3, Adams discloses application of the method to a subject displaying one or more clinical symptoms of inflammatory bowel disease (pg. 4, para. 4). Adams exemplifies symptoms including abdominal pain and diarrhea (pg. 1, para. 3), and further discloses that IBD is associated with numerous clinical symptoms that also present in other gastrointestinal disorders (pg. 1, para. 5).
Chang discusses diagnostic criteria for several IBS subtypes based on bowel habit, including IBS with diarrhea (pg. 25, para. 1), thereby teaching that diarrhea is a clinical symptom of at least one subtype of IBS. Chang also lists further symptoms of IBS including abdominal pain, and mentions an overlap in symptoms between IBS and IBD (pg. 19, para. 2).
Chang provides evidence that the particular IBD-associated symptoms exemplified by Adams include symptoms (i.e., abdominal pain and diarrhea) that are also associated with IBS. Thus, as evidenced by Chang, Adams discloses application of their method to subjects displaying clinical symptoms of IBS (that are also clinical symptoms of IBD).
With respect to claim 4, Adams discloses analysis of a plurality of, e.g., 100 or more, CpG sites (pg. 15, para. 5). In the same manner as detailed with respect to claim 1, the instant specification indicates that utilizing the microarray product exemplified by Adams comprises analysis of the recited CpG sites (e.g., cg11845159).
With respect to claim 5, Adams discloses performing bisulfite conversion using a kit for determination of methylation state (pg. 28, para. 4; pg. 39, para. 5 – pg. 40, para. 1).
With respect to claim 9, Adams discloses use of linear classification and/or machine learning techniques, i.e., algorithms, to classify the measured methylation data into groups including irritable bowel syndrome (pg. 18, para. 1; pg. 124, para. 3).
With respect to claim 13, Chang exemplifies various non-pharmacologic IBS treatments including cognitive behavioral therapy (pg. 21, para. 1).
With respect to claim 16, Adams discloses analysis of samples comprising blood, plasma, serum, intestinal cells or a biopsy, (pg. 28, para. 2). Adams further exemplifies analysis of methylation changes in intestinal mucosa (pg. 95, para. 1), and analysis of biopsies from mucosa (pg. 102, para. 4). In this way, Adams indicates that sampled intestinal cells or biopsies can constitute mucosal tissue.
With respect to claim 17, Adams discloses determining the methylation in DNA from mononuclear granulocytes, i.e., peripheral blood mononuclear cells including peripheral blood lymphocytes (pg. 4, para. 5 – pg. 5, para. 1).
With respect to claim 18, Chang teaches that at least 60 or 70% methylation at tested CpG sites provides evidence of irritable bowel syndrome (pg. 17, para. 3), therein teaching embodiments wherein the amount of biomarker methylation is greater than 54% of tested CpG sites.
An invention would have been obvious to one of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, said practitioner would have implemented analysis of methylation percentages, as taught by Chang, to enhance the diagnostic methods taught by Adams, because Adams discloses classification of subjects into groups, including IBS, based on comparison of measured methylation states but does not further describe specific steps for comparing the measured data while Chang teaches that comparing derived methylation percentages to disclosed thresholds (e.g., 60 or 70%) allows the user to differentially identify subjects having IBS (pg. 17, para. 3 – pg. 18, para. 1). Thus, the teachings of Chang provide a means for achieving a function required by Adams.
Additionally, said practitioner would have implemented administration of the identified treatments for IBS, as taught by Chang, to enhance the diagnostic methods taught by Adams, because Adams discloses classification of subjects into groups, including IBS, and selection of a treatment other than an anti-IBD treatment when subjects are not identified as having IBD, but does not exemplify any particular treatments other than anti-IBD treatments, while Chang teaches that the identified treatments are used to treat IBS (pg. 20, para. 2 - pg. 21, para. 1).
Said practitioner would have had a reasonable expectation of success because Adams and Chang both discuss methods of measuring and analyzing CpG site methylation to differentially classify subjects having related gastrointestinal disorders.
In this way the disclosure of Adams, in view of Chang, makes obvious the limitations of claims 1-5, 9, 13 and 16-18. Thus, the claimed invention is prima facie obvious.
Conclusion
At this point in prosecution, no claim is allowed.
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 Theodore C. Striegel whose telephone number is (571)272-1860. The examiner can normally be reached Mon-Fri 12pm-8pm ET.
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/T.C.S./Examiner, Art Unit 1685
/JESSE P FRUMKIN/Primary Examiner, Art Unit 1685 October 30, 2025
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