DETAILED ACTION
Applicant’s response, filed 05 Feb. 2026, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
Status of Claims
Claims 1-26 are cancelled.
Claims 27-38 are newly added.
Claims 27-38 are pending.
Claims 27-38 are rejected.
Priority
The effective filing date of the claimed invention is 15 April 2016, as discussed in the Office action mailed 01 Sept. 2023 (see para [009]-[013]).
Claim Interpretation
Claim 35 recites “…wherein the signature distinguishes subjects having Crohn’s Disease from subjects having ulcerative colitis using a Euclidean distance metric”. Claim 31, from which claim 35 depends, recites “making a diagnosis…based on the presence of said signature”. Therefore, in light of Applicant’s specification at para. ]0068], [0083], [00103], and [00109], claim 35 is interpreted to mean the diagnosis of Crohn’s disease (i.e. distinguishing subjects having Crohn’s disease) based on the signature uses a Euclidean distance metric.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 31-36 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention. This rejection is newly recited and necessitated by claim amendment.
Claim 31, and claims dependent therefrom, recite “(i)…determining the presence of a signature consisting of the identify and relative amounts of one or more nucleic acid oligomers, the signature distinguishing subjects having Crohn’s Disease from subjects not having Crohn’s disease”. The signature is selected from the group of signatures with oligomer(s) i) through xvii) at the bottom of the claim.
MPEP 2163.05 I. A. states under certain circumstances, omission of a limitation can raise an issue regarding whether the inventor had possession of a broader, more generic invention. See, e.g., Gentry Gallery, Inc. v. Berkline Corp., 134 F.3d 1473, 45 USPQ2d 1498 (Fed. Cir. 1998).
In the instant case, Applicant’s specification does not provide support for using the oligomer signatures i) through xvii) for distinguishing between subjects having Crohn’s disease and subjects not having Crohn’s disease, which encompasses using the signatures to distinguish between Crohn’s disease and healthy subjects, Crohn’s disease and cancer subjects, etc. Instead, Applicant’s specification at para. [0012], [0025]-[0027], [0048], specifically discloses using the signature to distinguish between subjects having ulcerative colitis (UC) or Crohn’s disease (CD). Applicant’s specification ([0060]-[0061]) specifically discloses using statistical analysis identified sets of features that allow for patients to distinguished from patients with ulcerative colitis. Applicant’s specification at para. [0016] also provides embodiments and specific signatures for distinguishing subjects having inflammatory bowel disease (IBD) (i.e. subjects with Crohn’s disease or ulcerative colitis) or not having IBD, which also does not support for specifically distinguishing a subject with Crohn’s disease in particular from any subject not having Crohn’s disease.
For the reasons discussed above, the specification does not provide a sufficient disclosure of the limitations of claims 31-36 above to demonstrate to one of ordinary skill in the art that the inventor possessed the invention at the time the application was filed. For more information regarding the written description requirement, see MPEP §2161.01- §2163.07(b).
Claim Rejections - 35 USC § 112(b)
The rejection of claims 9-11, 15, 16, 19, and 21 under 35 U.S.C. 112(b) in the Office action mailed 05 Sept. 2025 has been withdrawn in view of the cancellation of these claims received 05 Feb. 2026.
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.
Claims 27-30 and 36-38 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. This rejection is newly recited and necessitated by newly added claims.
Claim 27, and claims dependent therefrom, are indefinite for recitation of “(iii) making and recording a diagnosis of inflammatory bowel disease in the subject based on the presence of said nucleic acid oligomer”. Claim 27 previously recites “a presence of a signature consisting of the identify and relative amount of a nucleic acid oligomer” in (i) and “recording the presence, identity, and relative amount of said nucleic acid oligomer” in (ii). It is unclear if “the presence of said nucleic acid oligomer” is intended to refer to the presence of the signature (of the nucleic acid oligomer), which consists of the identify and relative amount, or if the presence of said nucleic acid oligomer is intended to refer to a different presence of the nucleic acid oligomer, such that “the presence of said nucleic acid oligomer” in steps (ii)-(iii) is not required to be closed to unrecited elements other than the signature consisting of the identify and relative amount of the oligomer. Dependent claim 29 is indefinite for the same reasons discussed above for claim 27 with respect to “the presence of said nucleic acid oligomer is determined by whole-genome shotgun sequencing”. Clarification is requested. For purpose of examination, (iii) is interpreted to refer to the presence of the signature consisting of the identity and relative amount of the nucleic acid oligomer. If Applicant agrees with this interpretation, claim 27 can be amended to recite “based on the presence of the signature of said nucleic acid oligomer”.
Claim 36 is indefinite for recitation of “comparing an abundance of the one or more signature nucleic acid oligomers…with an abundance of the signature nucleic acid oligomers…”.Claim 31, from which claim 36 depends recites “a signature consisting of the identity and relative amounts of one or more nucleic acid oligomers”, such that the signature is closed to unrecited elements other than the identity and relative amounts of the signature oligomers. As a result, it is unclear if the ”abundance” recited in claim 36 is required to be a “relative amount” or if the abundance can be any abundance, in which case, it is unclear if the signature used for the diagnosis is opened or closed to unrecited elements. For purpose of examination, the abundance of claim 36 will be interpreted to be a “relative amount”, consistent with claim 31.
Claim 37, and claims dependent therefrom, are indefinite for recitation of “making and recording a diagnosis…based on the presence of said nucleic acid oligomer” in (iii). Claim 37 previously recites “the presence, identify, and relative amount of said at least one nucleic acid oligomer” in (ii) and “the presence of a signature comprising the identify and relative amount of at least one nucleic acid oligomer” (e.g. also a presence of the at least one oligomer) in (i). As a result, it is unclear if the presence of the nucleic acid oligomer is the same as the presence of the signature of the at least one oligomer, or if this is a different presence. Clarification is requested. For purpose of examination, the diagnosis is interpreted to be based on the presence of the signature of the at least one oligomer that distinguishes the subjects having versus not having inflammatory bowel disease.
Response to Arguments
Applicant's arguments filed 05 Feb. 2026 regarding 35 U.S.C. 112(b) have been fully considered but they are not persuasive because they do not pertain to the new grounds of rejection set forth above.
Claim Rejections - 35 USC § 101
The rejection of claims 9-11, 15, 16, 19, and 21 under 35 U.S.C. 101 in the Office action mailed 05 Sept. 2025 has been withdrawn in view of the cancellation of these claims received 05 Feb. 2026.
Furthermore, claims 27-38 are patent eligible because the claims integrate the recited judicial exceptions into effecting a particular treatment for Inflammatory bowel disease and Crohn’s disease after applying the judicial exception to diagnose the subject with Inflammatory bowel disease (claims 27-30 and 37-38) or Crohn’s disease (claims 31-36).
Claim Rejections - 35 USC § 103
The rejection of claims 1, 3, 9, 11, 15, and 25-26 under 35 U.S.C. 103 as being unpatentable over Baran (2012) in view of Gillevet (2009) in the Office action mailed 05 Sept. 2025 has been withdrawn in view of the cancellation of these claims received 05 Feb. 2026.
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 37 is rejected under 35 U.S.C. 103 as being unpatentable over Baran (2012) in view of Gillevet (2009). This rejection is newly recited and necessitated by claim amendment.
Cited references:
Baran et al., Joint Analysis of Multiple Metagenomic Samples, 2012, PLoS Computational Biology, 8(2), pg. 1-11 (previously cited; cited in IDS filed 17 July 2018); and
Gillevet, US 2009/0197249 A1 (previously cited).
Regarding claim 37, Baran discloses a method for analyzing metagenomic samples using k-mer frequencies (Abstract; pg. 2, col. 1, para. 2), which comprises the following steps.
Baran discloses (i) identifying relative abundances of a plurality of k-mers characterizing sample component proportions (i.e. determining the presence of a signature comprising identities and relative amounts of one or more oligomers) (pg. 2, col. 1, para. 2; pg. 4, col. 1, para. 3, e.g. relative abundance xia; pg. 6, col. 1, para. 3; Figure 3), wherein the signature differentiates between samples that have Crohn's disease and Ulcerative colitis and healthy subjects (Table 1; pg. 6, col. 1, para. 3 to col. 2, para. 1, Figure 1), wherein the counts were determined from a microbiome sample of a subject (pg. 5, col. 2, para. 5). Baran further discloses the k-mer signature is determined from a population whole genome sequencing data from a plurality of patients with inflammatory bowel disease (pg.1, col. 1, para. 1 to col. 2, para. 2, e.g. whole-genome sequencing datasets; pg. 3, col. 1, para. 3-4, e.g. N samples with phenotype; pg. 5, col. 2, para. 5).
Baran discloses (ii) generating a matrix recording the relative occurrences of each k-mer for a sample (pg. 3, col. 2, para. 4, e.g. X = xia matrix, where xia is the relative abundance; pg. 6, col. 1, para. 3, e.g. each column is for a unique k-mer), which shows recording the presence, identity, and relative amounts of each k-mer.
Baran discloses (iii) using a regression model to classify the subject as having either ulcerative colitis or Crohn's disease (i.e. make a diagnosis of inflammatory bowel disease in the subject) (pg. 6, col. 1, para. 3 to col. 2, para. 4; Table 1, e.g. colitis and Crohn's predicted), wherein the classification is based on the presence of the signature of k-mers (Table 1;pg. 3, col. 1, para. 4; pg. 6, col. 1, par. 3 to col. 2, para. 1, e.g. pib represents proportion of component based on k-mer signature in the sample).
Regarding independent claim 37, Baran does not disclose the following limitations:
Regarding claim 37, Baran does not disclose that the presence, identities, and amounts of the at least one nucleic acid oligomer were recorded in electronic format. However, providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art.). See MPEP 2144.04. Thus automatically (i.e. in electronic format) recording the data does not distinguish over the manual generation of the data in a matrix in Baran.
Further regarding claim 37, Baran does not disclose (iv) administering to the subject diagnosed with inflammatory bowel disease one or more dietary or nutritional therapies, the therapies comprising enteral nutrition, parenteral nutrition, probiotics, prebiotics, and/or a low-residue diet.
However, regarding claim 37, Gillevet discloses a method for diagnosing colon disorders, including inflammatory bowel disease such as ulcerative colitis and Crohn’s disease in a subject (Abstract), and discloses determining a therapeutic regimen in the subject ([0016]) and administering probiotics to a subject with an inflammatory bowel condition to treat the inflammatory bowel disease ([0053]-[0054]).
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 Baran to have administered one or more drugs comprising antibiotics or initiating a probiotic therapy, as shown by Gillevet ([0016]; [0053]-[0054]). One of ordinary skill in the art would have been motivated to combine the methods of Baran and Gillevet to treat a subject diagnosed with an inflammatory bowel disease, including Crohn’s disease, as shown by Gillevet ([0053]-[0054]), thereby alleviating the disease in the subject, given Baran discloses classifying a subject as having ulcerative colitis or Crohn's disease (Table 1;pg. 3, col. 1, para. 4; pg. 6, col. 1, par. 3 to col. 2, para. 1). This modification would have a reasonable expectation of success given both Baran and Gillevet involve classifying/diagnosing inflammatory bowel conditions, and thus the treatment step of Gillevet is applicable to the classification of Baran.
Further regarding claim 37¸ Baran does not disclose the signature comprises an octamer(s) from the recited octamers in claim 37. Instead, Baran discloses detecting each possible 4-mer in the sample, as discussed above.
However, Baran discloses that in unsupervised component estimation, used to predict the presence of Crohn’s disease and ulcerative colitis (Table 1), we look for long k-mers whose abundance in sequencing reads of different samples correlate with a phenotype in question, and for large enough k, differences in the abundance of certain k-mers would capture differences in the abundance of specific species, genes, or functional domains (pg. 2, col. 1, para. 3). Baran further discloses that the abundance of k-mers, even for k as small as 3, varied between phenotypes (pg. 2, col. 2, para. 2), demonstrating smaller values for k may not differ between phenotypes. Baran further discloses performance of component estimation can be improved by extracting multiple k-mers per read when k is not too large by allowing the relative abundance of the k-mers to approach a constant value (i.e. to obtain a sufficient k-mer count) (pg. 4, col. 1, para. 2). Baran further discloses long k-mers with a length of 8 nucleotides are associated with particular phenotypes (pg. 3, col. 2, para. 3; pg. 6, col. 2, para. 3-4).
Thus, while in the disclosed embodiment, Baran uses k-mers signatures comprising k-mers of length 4 (pg. 3, col. 2, para. 3), 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 detected each possible 8-mers through routine experimentation of the value of k for the k-mers within the prior art conditions of increasing the length of the k-mers to sufficiently capture differences in the abundance of specific species, genes, or functional domains or decreasing the length of k to allow for the relative abundancies of the k-mers to approach a constant value (i.e. to allow for enough k-mers to be counted), as shown by Baran (pg. 2, col. 1, para. 3; pg. 2, col. 2, para. 2; pg. 4, col. 1, para. 2). See MPEP 2144.05 II. A.
Therefore, the invention is prima facie obvious.
Response to Arguments
Applicant's arguments filed 05 Feb. 2026 regarding 35 U.S.C. 103 as applicable to claim 37 above, have been fully considered but they are not persuasive.
Applicant remarks that Applicant disagrees with the Examiner’s analysis that it would have been obvious to detect each possible 8-mer through routine experimentation, and points out that the Examiner’s rejection rehash obviousness rejections already made and overcome by argument or amendment, noting a previous Office action said the claims were free of the prior art for recitation of specific oligomer signatures (Applicants’ remarks at pg. 14, para. 5 to pg. 16, para. 2). Applicant further remarks that the previous claims have been cancelled, and new claims 27-38 also recite specific sets of oligomers and therefore are free of the prior art (Applicant’s remarks at pg. 16, para. 3 to 5).
This argument is not persuasive. It is acknowledged that the rejection of the claims in the previous claim set were withdrawn for a specific set of oligomers. The set of oligomers was previously interpreted to be closed to unrecited elements, and thus the rejection was withdrawn because Baran makes obvious using a signature with every possible 8-mer, which includes unrecited 8-mers and does not read on the claims. In contrast, claim 37 recites “a signature comprising the identify and relative amount of at least one nucleic acid oligomer”, and thus the signature is open to unrecited oligomers. As a result, claim 37 is rejected over Baran in view of Gillevet because Baran in view of Gilevet make obvious using a signature with every possible 8-mer for diagnosing inflammatory bowel disease, as discussed above. Claims 27 and 31 recite “a signature consisting of the identify and relative amounts…”, and thus recite a signature that is closed to unrecited oligomers and are not rejected above.
Terminal Disclaimer
The Application is subject to a terminal disclaimer, filed 28 May 2025 and accepted 04 June 2025, over copending App. No. 15/028,253.
Conclusion
No claims are allowed.
Claims 27-36 and 38 are free of the prior art. The closest prior art of record, Baran, does not disclose the use of a signature consisting of the identity and relative amounts of a nucleic acid oligomer or one or more nucleic acid oligomers for distinguishing between subjects with and without Inflammatory Bowel Disease or Crohn’s disease, as recited in independent claims 27 and 31, or that the signature consists of the specifically recited oligomers recited in dependent claim 38. Baran in view of Gilevet make obvious using a signature with every possible 8-mer for diagnosing inflammatory bowel disease, as discussed above, which includes unrecited oligomers as part of the signature.
Claims 27-38 are patent eligible for the reasons discussed above.
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.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685