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 .
Election/Restrictions
Applicant's election with traverse of Group I, species in claim 4, in the reply filed on 6/2/2026 is acknowledged. The traversal is on the ground(s) that the claims of the methods and kit share the same or corresponding special technical. This is not found persuasive because the instant application is not a 371 application and therefore are not subject to unity of invention analysis. The requirement is still deemed proper for the reasons made of record in the previous office action and is therefore made FINAL.
Claim 12 is withdrawn from consideration as directed to a non-elected invention.
An action on the merits of claims 1-4, 6, and 8-10 are set forth herein.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide sequences appearing in the specification (see for example, tables 1 and 2) are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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 1-4, 6, and 8-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
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. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites a method of early risk assessment of preterm delivery of a subject based on the quantitative abundance of microbial markers sequences in a biological sample of the subject. This recitation is a natural correlation between microbial abundance and risk of preterm delivery. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites abstract ideas of early risk assessment, determining model scores, and performing risk assessment. See MPEP 2016.04 “Claims directed to nothing more than abstract ideas (such as mathematical algorithms), natural phenomena, and laws of nature are not eligible for patent protection". Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2). It is therefore determined that the claims recite judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of collecting a sample, extracting microbial DNA and determining quantitative abundance however this does not integrate the JE into a practical application because they are mere data gathering steps to use the correlation and do not add a meaningful limitation to the method. The recitation of “predetermined machine learning model”, “via one or more hardware processors” and “displaying via one or more hardware processors” do not describe any specific computational steps by which the computer performs or carries out the abstract idea or natural correlation, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than that a generic computer performs the functions that constitute the abstract idea and natural correlation. Hence, these are mere instructions to apply the abstract idea and natural correlation using a computer, and therefore the claim does not integrate the JEs into a practical application
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the step of obtaining a sample or extracting nucleic acids is considered insignificant post solution activity. The steps of determining quantitative abundance using quantitative PCR is generally recited and does not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). The mere instructions to implement the abstract idea or natural correlation using a computer are, when considered individually, insufficient to constitute an inventive concept that would render the claims significantly more than an abstract idea (see MPEP 2106.05(f)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
Additionally, when viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists using abstract ideas. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112
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 1-4, 6, and 8-10 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.
The recitation of “predetermined machine learning model” and “predetermined threshold value” along with “associated to the biological sample” is unclear because the relationship between the model, threshold, and the biological sample is not clear. For example, is the biological sample used to generate the model, is it used to generate the threshold, or is the sample compared to the threshold use the model? Appropriate correction is required for all claims.
The claims are generally narrative and indefinite, failing to conform with current U.S. practice and are replete with grammatical and idiomatic errors. For example, claims 4, 6, 10 depend from claim 1 and use the present participle “being” whereas the remainder of the claims use the past participle. Additionally, “the biological sample being a stool sample” lacks sufficient antecedent basis because claim 1 does not recite a stool sample. This example applies to all of the claims and the guidance therein should be used to amend all of the necessary claims.
Claims 4 and 6 are incomplete because they refer to a table. Additionally, the reference to Gut_seq should be amended to recite instead the SEQ ID NOS for each Gut sequence from table 1. As set forth in the MPEP 2173.05(s):
Reference to Figures or Tables
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Claim 4 would be clearer if it were amended to recite, “The method according to claim 3, wherein the microbial marker sequences associated with the biological sample comprise each of SEQ ID NOS: 9 and 11-24.” since claim 3 limits the biological sample to a stool sample. Appropriate correction of all claims (e.g. claim 6) is required.
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 1, 2, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Park I (Park et al; American Journal of Reproductive Immunology; 2021; 00:313435, pages 1-9).
Park teaches a method of assessing the risk of preterm delivery (abstract, whole document) collecting a biological sample from the subject whose risk of preterm delivery is to be assessed, extracting DNA from the biological sample, determining a quantitative abundance (table 2) of each of a plurality of predetermined microbial marker sequences from the extracted DNA sequences (page 2), using a set of probes specific to each of the plurality of predetermined microbial marker sequences with multiplexed quantitative Polymerase Chain Reaction ( (pages 2-4), determining, via one or more hardware processors, a model score based on the quantitative abundance of each of the plurality of predetermined microbial marker sequences in the biological sample using a pre-determined machine learning (ML) model (page 4-7, table 4) performing, via the one or more hardware processors, the early risk assessment of preterm delivery in the subject (pages 4-7, table 2) based on the model score and a predefined threshold value associated with the biological sample. Although Park does not teach displaying via one or more of the hardware processors, the early risk assessment of in the subject, it would have been prima facie obvious to display the risk for a subject so as to inform practitioners and the subject of the risk of preterm delivery. Park teaches determining different risk groups, therefore it would have been prima facie obvious to the ordinary artisan to have further assessed antibiotics for the treatment of microbial infection to reduce the risk of preterm delivery.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Park I as applied to claims 1, 2, and 9 above, and further in view of Mande (Mande et al; US 11,062,808).
The teachings of Park I are set forth above. Park I does not teach obtaining a biological sample that is stool. However, Mande teaches a method of assessing risk of preterm delivery in a subject by obtaining a stool sample, and determining the taxonomic abundance of microbial DNA in the sample (see abstract, figures, claims). Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have used stool samples as taught by Mande for assessment of microbial DNA abundance in the method of Park I because Mande teaches that stool samples can be used to assess preterm delivery.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Park I as applied to claims 1, 2, and 9 above, and further in view of Park II (Park et al; Frontiers in Microbiology,10.3389/fmicb.2022.912853; pages 1-11).
The teachings of Park I are set forth above. Park I does not teach an ensemble ML model, however Park II teaches a method of assessing risk of preterm birth using microbial biomarkers. Park II teaches using multiple machine learning models (see abstract, pages 3-6; and teaches that preterm delivery prediction models were trained based on five machine learning methods to validate prediction models for performance on future patients. Therefore, it would have been prima facie obvious prior to the effective filing date to have included validation with different machine learning models, as taught by Park II for the obvious benefit of constructing a model for use with future patients.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Winston Shen, can be reached at (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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