DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed May 5, 2026. Currently, claims 1-12, 15-16 are pending. Claim 12 has been withdrawn as drawn to non-elected subject matter.
Election/Restrictions
Applicant's election without traverse of Group 1, Claims 1-11, 15-16 and SEQ ID NO: 1 and 6 in the paper filed May 5, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application claims priority to
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Drawings
The drawings are acceptable.
Sequence Rules
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Nucleotide sequences appear on at least pages 11, 16 and 17 of the specification and are not identified by SEQ ID NO:.
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.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Pages 27-31 of the specification provide a list of references.
Claim Objections
Claim 6 is objected to because there is text following the period. Periods are used to denote the end of the claim. After Claim 6, “-2” is recited. It is unclear what this text relates to.
Improper Markush Rejection
Claims 5-6, 15-16 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
A Markush claim contains an “improper Markush grouping” if:
(1) the species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent. See MPEP § 2117.
Here each species is considered to each of the colorectal cancer biomarker genes listed in Table II.
The recited alternative species in the groups set forth here do not share a single structural similarity, as each different sequence that could be detected is itself located in a separate region of the genome and has its own structure and detects a different gene in a different species. The genes recited in the instant claims, do not share a single structural similarity since each consists of a different nucleotide sequences with different detection patterns. The only structural similarity present is that all detected positions are part of nucleic acid molecules. The fact that the markers comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity.
MPEP 2117 (II)(A) provides the following guidance as to what constitutes a physical, chemical, or art recognized class:
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved”
The recited genes do not belong to a recognized chemical class because there is no expectation from the knowledge in the art that the genes will behave in the same manner and can be substituted for one another with the same intended result achieved. In other words, there is no expectation from the knowledge in the art that each of the recited genes would function in the same way in the claimed method; it is only in the context of this specification that it was disclosed that all members of this group may behave in the same way in the context of the claimed invention. Further there is no evidence of record to establish that it is clear from their very nature that each of the recited genes possess the common property of being associated with any particular disease or condition.
MPEP 2117 (II) further states the following:
Where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the compounds do not appear to be members of a recognized physical or chemical class or members of an art-recognized class, the members are considered to share a "single structural similarity" and common use when the alternatively usable compounds share a substantial structural feature that is essential to a common use. Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The recited alternative species do not share a substantial common structure just because they all have a sugar phosphate backbone. The sugar phosphate backbone of a nucleic acid chain is not considered to be a substantial common structural feature to the group of genes being claimed because it is shared by ALL nucleic acids. Further, the fact that the genes all have a sugar phosphate backbone does not support a conclusion that they have a common single structural similarity because the structure of comprising a sugar phosphate backbone alone is not essential to a common use.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
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 9-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
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, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claims 9-11 are directed to “a method for in vivo profiling of a complex microbiome” for “identifying relationships” or “for identifying microbial composition and functions in the mouth….” Or for “identification of a diet or therapy for treatment of a disease…”. While the claims do not currently recite an active process step for accomplishing these methods, the recitation is still a judicial excpetion as it recites a natural law and abstract idea.
Claims 9-11 are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “for “identifying relationships” or “for identifying microbial composition and functions in the mouth….” Or for “identification of a diet or therapy for treatment of a disease…”) and a law of nature/natural phenomenon (i.e. the natural correlation between the RNA profile and the recited diseases or disorders).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, claim 21 involves the patent-ineligible concept of an abstract process. Claim 21 requires performing identification of microbial compositions and functions or identification of a diet or therapy of a disease or disorder. Neither the specification nor the claims set forth a limiting definition for "identifying" and the claims do not set forth how “identifying” is accomplished. As broadly recited the identifying step may be accomplished mentally by thinking about a subject’s RNA profile and assessing whether the subject has a disorder or disease. Thus, the identifying constitutes an abstract process idea.
A correlation that preexists in the human is an unpatentable phenomenon. The association between RNA profiles and risk of diseases, disorders or cancer is a law of nature/natural phenomenon. The identifying which tells users of the process to predict diseases, disorders or cancer in the sample, amounts to no more than an "instruction to apply the natural law". The identifying is no more than a mental step. Even if the step requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The identifying does not require the process user to do anything in light of the correlation. The "assessing" step fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.”
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites obtaining a sample and RNA sequencing, this is not an integration of the exception into a practical application. Instead these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The RNA profiling on the sample by multiplex RNA sequencing is mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the RNA profile of a sample without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The RNA profiling was well known in the art at the time the invention was made. As evidenced by the 102 rejections below the art teaches RNA profiling on complex samples. The steps are recited at a high level of generality. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112- Second Paragraph
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 1-11, 15-16 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 pre-AIA the applicant regards as the invention.
A) Regarding claims 1, 4, 15-16, the phrase "preferable" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
B) Claims 5, 6, 15-16 refers to tables. MPEP 2173.05(s) states:
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).
Claims 5, 6, 15-16 recites Table II. Appropriate correction is required.
C) Regarding claims 10-11, the phrase "such as" and “including” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
D) Claims 9-11 are directed to intended uses for the method of Claim 1. The claims do not recite any additional method steps but merely provide the intended use for the method. It is unclear what additional steps are required for the method to produce the intended outcome.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis 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.
Claim(s) 1-4, 7-11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Leenders (US 2020/0032347, January 30, 2020).
Leenders teaches a method of RNA next generation sequencing-based profiling to detect nucleic acids in a complex microbiome. Leenders teaches Leenders teaches the method may be used to provide personalized treatment with drugs targeting diseases.
With respect to Claim 2, Leenders teaches using molecular inversion probes for profiling and multiplex RNA sequencing (see Figure 1, para 29).
With respect to Claim 3, Leenders teaches the RNA of interest may be pathogenic bacteria (see para 31).
With respect to Claim 7, Leenders teaches analysis of gene encoding enzymes involved in tyrosine metabolism such as tyrosine kinase (see Figure 3, para 18, 23).
With respect to Claim 8, Hyman teaches designing smMIPs for detection of hrHPV transcripts E2, E6 and E7.
Claims 9-11 are directed to intended uses for the method of Claim 1. Claims 9-11 do not add any additional method steps. Regardless, the method of Hyman is directed to identifying relationships of microbial species and cancers including cervical cancer, head and neck cancers.
Claim(s) Claims 1, 3, 4, 7-11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Macklaim et al. (Microbiome, Vol. 1, No. 12, pages 1-11, 2013).
Macklaim teaches a method for profiling a complex vaginal microbiome by obtaining a sample, RNA profiling using multiplex RNA sequencing. In particular Macklaim teaches obtaining vaginal swabs from women (i.e. a sample comprising a complex microbiome)(limitations of Claim 4). Macklaim teaches performing RNA profiling using RNA-seq to obtain reads. Mackalim teaches analysis of bacteria including Lactobacillus iners (limitations of Claim 3).
With regard to Claim 4, the sample is from the cervicovaginal area (page 8, col. 1).
With regard to Claim 7, Maclaim teaches analysis of the genome which comprises the genes encoding enzymes involved in metabolism and rRNA genes.
With regard to Claim 8, Figure 1 illustrates the gene discriminate microbial genus and species. Macklaim teaches the highly expressed cpn60 gene is nearly universally conserved in bacteria and contains a variable sequence which allows for taxonomic discrimination (page 2, col. 1).
Claims 9-11 are directed to intended uses for the method of Claim 1. Claims 9-11 do not add any additional method steps. Regardless, the method of Macklaim is directed to identifying relationships of microbial species and cervovaginal malignancies.
Claim 1- 4, 8-11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hyman et al. (Microbiology, Vol. 12, No. 29, pages 1-10, 2012).
Hyman teaches molecular probe technology to detect bacteria. Hyman teaches methods of multiplexing for detection of bacteria in vaginal swabs. Hyman teaches using Affymetrix GenFlex Tag 16K arrays for sequencing by oligonucleotide ligation and detection (abstract).
With respect to Claim 2, Hyman teaches using molecule inversion probes that hybridize to regions of a target to form circular structures (Figure 1, page 2).
With respect to Claim 3, Hyman teaches analysis of bacteria.
With respect to Claim 4, Hyman teaches analysis of vaginal swabs.
With respect to Claim 8, Hyman teaches analysis to discriminated bacterial genus and species (see Table 1).
Claims 9-11 are directed to intended uses for the method of Claim 1. Claims 9-11 do not add any additional method steps. Regardless, the method of Hyman is directed to identifying relationships of microbial species and cervovaginal malignancies.
Conclusion
No claims allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Androlojc et al. (BMC Biology, Vol. 19, No. 267, December 2021) teaches high-resolution targeted sequencing of the cervicovaginal microbiome. This is applicant’s own post filing date work.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached on (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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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
July 7, 2026
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