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 .
Status of the Application
The Response filed December 19, 2025 is acknowledged.
Claims 1-20 were pending. Claims 12, 14-15, 17, 19-20 and new claims 21-22 are being examined on the merits. Claims 1-11, 13, 16 and 18 are canceled.
Response to Arguments
Applicant’s arguments filed December 19, 2025 have been fully considered.
The following objections and rejections are WITHDRAWN in view of Applicant’s arguments and amendments to the specification and claims:
Objections to the Specification
Objection to claims 9 and 20
Rejection of claims 6 and 17 under 35 USC § 112(b), indefiniteness
Rejection of claims 6 and 17 under 35 USC § 112(d)
Rejection of claims under 35 USC § 101
Prior art rejections of claims 1-11, 13, 16 and 18
Response to arguments regarding 35 USC § 101 rejections
The prior art rejections are withdrawn because independent claim 12 has been amended to require the particular treatment of “microbiome augmentation”. The instant specification teaches that “microbiome augmentation” comprises a group of treatments including administering fecal augmentation therapy, antibiotics, prebiotics, probiotics, metabolite supplementation, microflora replacement therapy or microbiota-derived metabolites (e.g., p. 19, ll. 11-13).
The following rejections are MODIFIED in view of the instant claim amendments:
Prior art rejections of claims 12, 14-15, 17, 19-20
Response to arguments regarding prior art rejections
The prior art rejections have been modified in view of the instant amendments. However, to the extent that Applicant’s arguments relate to the modified rejections, the Examiner notes the following.
Applicant argues that the prior art rejections should be withdrawn because independent claim 12 has been amended to require, first, that the one or more biomarkers is measured in a sample obtained from a subject 30 days or less prior to surgery, and, second, that the one or more biomarkers is measured to determine the risk of post-surgical infection. Applicant argues that Abrams is generally directed to methods involving assessing patients in the ICU, and does not teach or suggest either of the instantly amended limitations (Remarks, pp. 6-7).
The Examiner disagrees. As noted below in the prior art rejections, Abrams teaches obtaining a sample from the subject admitted to the surgical ICU at 4 hours post-admission, and again 72 hours later. Abrams does not teach when these sampling periods are relative to surgery, however, patients may be admitted to the surgical ICU either before or after surgery (see Strada, below). Abrams further teaches that testing prior to a procedure (specifically, bone marrow transplant, which is perhaps not a surgical procedure, per se), is useful for assessing the risk of bacteremia, respiratory infections and death (para. 573). Further, Abrams teaches that subjects include critically ill immunosuppressed patients, such as a solid-organ transplant recipients. The ordinary artisan understands that a subject who is the recipient of a solid-organ transplant is post-surgery (paras. 35, 43). Thus, at a minimum, Abrams suggests the instantly amended limitations.
Applicant also argues that the rejection of claim 15 should be withdrawn because Abrams does not teach or suggest measuring Enterobacterales species to determine post-surgical infection risk (Remarks, p. 7). Applicant also argues that Abrams teaches measuring Enterococcus species, but teaches that ICU patients demonstrate a wide range of relative abundance. Applicant further argues that Abrams does not teach that a relative abundance of 19.9% is a critical threshold as it is associated with a high sensitivity and specificity for determining post-surgical infection risk, and which provides certain technical achievements as compared to the methods in the cited references (Remarks, p. 7).
The Examiner disagrees. First, as to measuring Enterobacterales, the prior art rejections do not cite Abrams for teaching measuring Enterobacterales, and further measuring Enterobacterales is not a required limitation of the instant claims. Second, as to the 19.9% relative abundance value in claim 15, it is noted that claim 15 depends from claim 14, which recites, in part, determining that the subject is at risk of developing a post-surgical infection when the relative abundance of Enterococcus species is greater than or equal to a threshold value. Thus, claim 14 is reciting a range of Enterococcus relative abundance associated with a risk of developing a post-surgical infection, but where neither the lower nor the upper limit is described with a numerical value. Claim 15, in turn, recites that the threshold value is 19.9%. Thus, claim 15, which incorporates all of the limitations of claim 14, is directed to a range of Enterococcus relative abundance associated with a risk of developing a post-surgical infection, where the lower end of the range is 19.9%, but the upper limit is unspecified. The broadest reasonable interpretation of claim 15 does not require that the assay have any particular sensitivity or specificity, nor does the claim require identifying a threshold value of 19.9% per se, but rather merely requires “determining that the subject is at risk … when … the relative abundance is … greater than or equal to 19.9%”. Also see MPEP 2145 II, which states that “[m]ere recognition of latent properties … does not render obvious an otherwise known invention”. Further, the art does not have to teach the endpoints of a range in order to anticipate a range. Rather, when a claim covers several compositions, the claim is anticipated if one of them is in the prior art (MPEP 2131.03). Thus, if the prior art teaches any value in the range of 19.9% to [unspecified upper limit], then the art anticipates the claim 15 range.
These arguments are not persuasive. The rejections are modified to account for the instant claim amendments.
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.
Claims 12, 14-15, 17 and 19-22 are rejected under 35 U.S.C. 103 as being unpatentable over Abrams1 (US Patent App. Pub. No. 2020/0030366 A1) in view of Chen (Biomarker Assay Development, Qualification and Validation. In: Fang, L., Su, C. (eds) Statistical Methods in Biomarker and Early Clinical Development. Springer, Cham. 2019 https://doi.org/10.1007/978-3-030-31503-0_6), as evidenced by Akamatsu2 (Primary biliary cirrhosis and liver transplantation, Intractable Rare Dis Res., 1(2):66-80, 2012) and as evidenced by Strada (Patient education series: understanding trauma and emergency surgical conditions – understanding surgical intensive care units (SICU), Trauma Surg Acute Care Open, 10(4), 1-2, 2025).
Regarding independent claim 12 and dependent claims 21-22, Abrams teaches …
A method comprising (a) measuring a level of one or more microbiomics biomarkers
and/or one or more metabolomic biomarkers in a fecal sample obtained from a subject, optionally a mammal or human, to determine a risk of post-surgical infection in the subject. Specifically, Abrams teaches that loss of colonization resistance is a risk factor for ICU-acquired infections, and that fecal microbial diversity is a proxy measure for colonization resistance (paras. 75-78, 168, 184). Abrams also teaches that short-chain fatty acids (SCFAs) are key to colonization resistance, and that the depletion of SCFAs correlates with pathogen colonization (paras. 4, 6, 77).
Regarding the limitation reciting that the sample is obtained from the subject within 30
days or less prior to surgery, Abrams does not explicitly teach that the sample is obtained at a certain time point relative to surgery, but does teach that the samples are collected shortly after patients arrive in surgical ICU, which the ordinary artisan would understand to be around the time of surgery (para. 547: patients admitted to surgical ICU; rectal swabs taken within 4 hours of admission and 72 hours later). Further, as evidenced by Strada, patients may be admitted to the surgical ICU before or after surgery (p. 1, right col., para. 5: “[i]f surgery is needed, the timing and type depend on the patient’s condition. The SICU team works with surgeons to decide the best plan. After surgery, patients may return to the SICU …”). Abrams additionally teaches testing prior to a procedure (para. 573: bone marrow transplant), and teaches that subjects include solid-organ transplant recipients. The ordinary artisan understands that a subject who is the recipient of a solid-organ transplant is post-surgery (paras. 35, 43). Thus, since Abrams teaches that the sample is obtained shortly after patients arrive in the surgical ICU, and since patients may be admitted to the surgical ICU before or after surgery, and in view of these additional teachings, Abrams, at least, suggests that the sample is taken within 30 days or less prior to surgery. Further, to the extent that the Abrams assays comprise steps or components that are actually completed at a time other than 30 days or less prior to surgery, the ordinary artisan would be know how to modify those steps or components, as taught by Chen (e.g., section 3: consideration in assay development; section 4: analytical method validation; section 5: consideration of clinical characteristics), to arrive at steps or components that are relevant to the chosen time of sampling.
Abrams additionally teaches (b) providing microbiome augmentation to the subject determined to be at risk of developing a post-surgical infection (paras. 35, 122);
wherein (i) measuring a level of one or more microbiomics biomarkers comprises measuring a relative abundance of Enterococcus species (paras. 4, 27, 269);
or (ii) the one or more metabolomic biomarkers are acetate and butyrate (para. 269).
Prior to the effective filing date of the instant invention, it would have been prima
facie obvious to modify the Abrams method to collect the sample within 30 days of surgery. Abrams does not explicitly teach that the sample is obtained at a certain time point relative to surgery, but does teach that the samples are collected shortly after patients arrive in surgical ICU, which the ordinary artisan would understand to be around the time of surgery. Thus, it would have been obvious for the ordinary artisan to try the Abrams method by collecting the sample within the recited time frame with the expectation that doing so would result in the advantage of a useful prognostic tool for patients immediately following surgery, and which would allow for prophylactic treatment of the patient prior to surgery. The ordinary artisan would have had an expectation of success as Abrams teaches that the method is useful in patients that are hospitalized for surgery, and because Chen teaches how to design and modify biomarker assays.
Regarding dependent claims 14-15, Abrams additionally suggests that the relative
abundance of the Enterococcus species is greater than or equal to a threshold value, specifically 19.9%. Specifically, Abrams teaches various parameters associated with Enterococcus relative abundance levels (paras: 4, 27, 269, 32; Fig. 9A, no fiber group, shows instances of relative abundance (expressed as a proportion) of Enterococcus above 0.199; para. 200: relative abundance of 22%). As noted above, to the extent that the Abrams assays comprise steps or components that are actually completed at a time other than 30 days or less prior to surgery, the ordinary artisan would be know how to modify those steps or components, as taught by Chen (e.g., section 3: consideration in assay development; section 4: analytical method validation; section 5: consideration of clinical characteristics), to arrive at steps or components that are relevant to time of sampling.
Regarding dependent claim 17, Abrams additionally suggests that levels of acetate and
butyrate in the fecal sample that are decreasing relative to a threshold value indicates that the subject is at risk of developing a post-surgical infection (para. 269). Specifically, Abrams teaches various parameters associated with metabolomic biomarker levels (paras: 4, 30-31, 269). As noted above, to the extent that the Abrams assays comprise steps or components that are actually completed at a time other than 30 days or less prior to surgery, the ordinary artisan would be know how to modify those steps or components, as taught by Chen (e.g., section 3: consideration in assay development; section 4: analytical method validation; section 5: consideration of clinical characteristics), to arrive at steps or components or treatments that are relevant to time of sampling.
Prior to the effective filing date of the instant invention, it would have been prima
facie obvious to incorporate into the modified Abrams method, discussed above, various modified parameters associated with the biomarker levels. It would have been obvious for the ordinary artisan to do so in order to optimize the assay as needed through routine experimentation, and would have had an expectation of success as Chen teaches how to design and modify biomarker assays.
Regarding dependent claim 19, Abrams additionally teaches that the surgery is an organ
transplant (paras. 35, 45).
Regarding dependent claim 20, Abrams additionally suggests that the organ transplant
is a liver transplant. Specifically, as noted, Abrams teaches organ transplant and also teaches patients with, e.g., primary biliary cirrhosis (para. 112), which can be treated with a liver transplant (as evidenced by Akamatsu, abstract).
Prior to the effective filing date of the instant invention, it would have been prima
facie obvious to further modify the modified Abrams method, discussed above, so that it is used in conjunction with a liver transplant. Abrams teaches that the assay is useful for identifying infection risk in patients undergoing various surgeries, including organ transplants, and teaches that the assay is useful for identifying infection risk in patients with conditions for which a liver transplant is an appropriate treatment. Thus, it would have been obvious for the ordinary artisan to try the Abrams method with liver transplant patients with the expectation that doing so would result in the advantage of a useful prognostic tool for liver transplant patients. The ordinary artisan would have had an expectation of success as Abrams teaches that the method is useful in organ transplantation situations.
Conclusion
Claims 12, 14-15, 17 and 19-22 are being examined and are rejected. No claims are 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 CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 Abrams was cited in the PTO-892 Notice of References Cited mailed October 2, 2025.
2 Akamatsu was cited in the PTO-892 Notice of References Cited mailed October 2, 2025.
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