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 .
Application Status
Amended claims were filed on 12/15/25 and claims 1-5, 7-11, 21-27 are under consideration. Claims 17-20 are withdrawn. Claims 6, 12-16 are cancelled. Past correspondence addresses the invention and species elections.
The Specification objection, as well as Claim 9 and Claim 12 objections are withdrawn in view of amendment or cancelled claims. The 35 USC § 112(b) rejections of claims 1-16 are withdrawn in view of amendment or cancelled claims. The 35 USC § 112(a) rejection of claims 1-16 is withdrawn in view of amendment or cancelled claims. It is noted that the 35 USC § 101 rejection is modified in view of amendments and maintained (below).
Response to Remarks: The majority of remarks (Pg 1-9) pertain to amended/cancelled claims and since most of the rejections have been withdrawn, no further comment is necessary for these. Applicant, Pg 11, indicates that the 101 rejection (natural correlation) over claim 1 should be withdrawn because diagnosing MI based on gut microbiota is integrated with the specific primer pair recited. The amended claim however remains drawn to a correlation and the primers are known in the art and amplify a commonly referenced region, and in the subsequent analysis steps, the primers do not rise above the concepts that would obviate the rejection.
Subsequent to these comments, the remainder of the Remarks address newly proposed claims and why these should be patent eligible. These Remarks have been considered.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 26 and 27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 is indefinite in the recitation of “using a primer set of (1) SEQID NO: 21 and SEQID NO: 22, (2) SEQID NO: 23 and SEQID NO: 24, (3) SEQID NO: 3 and SEQID NO: 4, (4) SEQID NO: 25 and SEQID NO: 26, or a mixture thereof. As stated, it is not clear to what “or a mixture thereof” refers.
Claims 26 and 27 are indefinite in the recitation of in the recitation of “the features” of bacterial taxa. Said features are not defined in the Specification and it is not clear how to establish the metes and bounds of what does and does not constitute a feature.
Claims 26 and 27 are indefinite over the recitation of “performing supervised machine learning classifiers on the features”, which is unclear as stated. Is this intended to reference for example, use to train or development or application of classifiers, or something entirely different. In this same phrase, is the recitation, “on the features of the bacterial taxa on the gut microbiota” which is unclear in meaning, as recited.
Claim Rejections - 35 USC § 101 – modified and maintained in view of amendments
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5,7-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
While the instant claims are directed to a valid statutory category (Step 1, Statutory Category Analysis) of a method, the claims recite a law of nature (Step 2A, Prong One, Judicial Exception Analysis), or a natural correlation between MI in a human, monkey or mouse subject and increased abundance of gut Strep., Clostridium and/or Butrycimonas relative to a control, without MI. As discussed in MPEP 2106.04(b)(II), the correlation includes naturally occurring products, here bacterial abundance. Further, regarding laws of nature, their unpatentability was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012). “Laws of nature, natural phenomena, and abstract ideas” are not patentable. Diamond v. Diehr, 450 U.S. 175, 185 (1981); see also Bilski v. Kappos, 561 U.S. 593, 604, 95 USPQ2d 1001, 1007 (2010).
However, the judicial exception, or correlation, is not integrated into a practical application (MPEP 2106.04(d)), (Step 2A, Prong Two Integration into Practical Application Analysis) as for example, there is not particular treatment or particular prophylaxis effected (MPEP 2106.04(d)(2)), or improvement in computer functioning or technology, or transformation/reduction of particular article to a different state/thing (MPEP 2106.04(d)(1)).
Further, the claimed additional elements, where present, do not add a meaningful limitation to the method and therefore constitute that which is considered to be insignificant extra-solution activity or routine and conventional steps (Step 2B, Inventive Concept, Significantly More Analysis), as will be shown here.
For claims 1 and 2, obtaining a sample of gut microbiota is routine (e.g. Pg 649, right col, 1st full para of Tang et al., Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair, 2019, Circulation, 139 647-659; Pg 649, left col, 3rd full para, hereafter Tang) as is performing 16S genetic analysis (e.g. for 16S rDNA analysis see Pg 649, right col, 1st full para of Tang; for 16S rRNA analysis of human microbiome demonstrating enriched genes in patients versus healthy controls, see Vital et al. (Vital, M. et al., A gene-targeted approach to investigate the intestinal butyrate producing bacterial community, Microbiome, 2013, 1:8; Abstract); for analyzing 16S rRNA of gut (Liu, Pg 2, Abstract, line 25-26 and 32-33, Liu, P-Y. et al, Evaluation of compatibility of 16S rRNA V3V4 amplicon libraries for clinical microbiome profiling, 2020, bioRxiv, Pg 1-46).
For use of primers, SEQID 29 and 30 (V3-V4) for 16S rRNA work, in human gut metagenome studies, and for qPCR methods, see Sardu (10/6/2020, ClincialTrials.gov, NCT03439592, Analysis of the Microbiota of STEMI, Pg 4, para 2), also regarding primers for analyzing V3-V4 of 16S rRNA for analyzing bacterial diversity (Pg 2 right col final para; Fadeev et al, Comparison of two 16S rRNA primers (V3-V4 and V4-V5) for studies of arctic microbial communities, Feb 2021 12:1-11; and Pg 4, Sims et al., Gut microbial diversity and genus-level differences identified in cervical cancer patients versus healthy controls, 2019, Gynecol Oncol 155:237-244) and particularly for 16S rRNA studies of Streptococcus abundance in human gut (see Jones, R. et al, High intake of dietary fructose in overweight obese teenagers associated with depletion of Eubacterium and Streptococcus in gut microbiome, 2019, Gut Microbes 10: 6:712-719; Abstract, Pg 717 left col first para). Further, it is also noted that primer development, and PCR, qPCR, RT-PCR are considered routine and conventional activities in molecular biology.
Re: Claims 3 and 4, claim 3 recites qPCR with primers which are well known in the art (e.g., Chen below, disclosed S. parasanguinis primers), and claim 4, further natural correlations and methods that involve the use of 16S rRNA for decreased gut abundance determination of bacteria, including Bifidobacterium, which are known (Pg 715, left col, para 2 of Jones; Abstract, Matsuki et al., Distribution of Bifidobacterial species in human intestinal microflora examined with 16S rRNA-gene-targeted species specific primers, 1999, 4506-4512; ) and claim 5 similarly addresses natural bacterial abundance. While primer construction is routine in the art, there is data demonstrating that S. parasanguinis primers have been developed (Chen, Q. et al., Quantification of human oral and fecal Streptococcus parasanguinis by use of quantitative real-time PCR targeting the groEL gene, 2019, Front Micb 2019, 10: 1-14, Abstract).
Re: claims 7-9, claims 7 and 8 recite next generation sequencing of 16S rRNA on gut microbes which is routine (e.g. 16S rRNA sequencing and16SrDNA V4 amplicons were sequenced on a MiSeq, which is next generation sequencing, performed by Sims, Pg 3 final para). Further, for Claim 8, conducting analysis via LDA and claim 9, analysis via alpha/beta diversity, are routine and conventional analyses that involve the use of mathematical calculations that have been performed in the art for similar purposes, including by Sims (Pg 4, para 2), and therefore constitute mere data gathering, and the application of mathematical concepts, also considered mental processes that amount to abstract ideas since the calculation relies upon the application of a mathematical formulae and can be performed with the mind, where notably performed by humans versus on a computer are not distinguished from one another (MMPEP2106.04(a)III. As such these claims are patent ineligible (see “mathematical concepts” group of abstract ideas, MPEP 2106.04(a) and MPEP 2106.04(a)(2)).
Claim 10, obtaining control samples’ gut microbiota, Tang addressed gut microbiota and compared data of control and probiotic treated mouse subjects (Pg 649, left col final para to right col top line), with consideration of healthy mice for propionate supplementation (Pg 656 right col, penultimate para).
Claim 11 incorporates a particular type of MI, STEMI, for the early detecting or diagnosing, predicting prognosis or treatment outcome and/or differentiating of claim 1, which does not modify the judicial exception, or natural correlation identified between MI and bacterial abundance.
In sum, claims 1-11 constitute judicial exceptions, without significantly more, and are not integrated into a practical application (see MPEP 2106.04(d)(2)). Thus, under 35 U.S.C. 101 these claims are patent ineligible.
Conclusions
Claims 1-5, 7-11, 26 and 27 are rejected. Claims 21-25 are allowable.
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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/LISA HORTH/Examiner, Art Unit 1681
/GARY BENZION/Supervisory Patent Examiner, Art Unit 1681