DETAILED ACTION
Applicant’s response, filed 07/28/2026, has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. 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 .
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 Status
Claims 125, 127, 129-135, 140, 142, 144-146, and 150-155 are pending.
Claims 1-124, 126, 128, 136-139, 141, 143, 147, and 148 are canceled.
Claims 150-155 are newly added.
Claims 125, 127, 129-135, 140, 142, 144-146, and 150-155 are rejected.
Priority
This application 17772832 filed on 04/28/2022 is a 371 national phase of, PCT/US2020/058382, filed 10/30/2020, which claims domestic benefit to US provisional application 63/061,709 08/05/2020 and domestic benefit to US provisional application 62/930,465 11/04/2019 and claims domestic benefit to US provisional application 62/929,579 11/01/2019. The priority date of claim 125 and its dependent claims is determined to be 10/30/2020, the filing date of PCT/US2020/058406 because none of each of the three provisional applications 62/929,579; 62/930,465; and 63/061,709 fully supports the steps (a)-(d) recited in amended claim 125 filed on 03/06/2026.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 07/15/2022, 12/13/2023, 11/13/2024, 07/09/2025, 03/06/2026, and 08/03/2026 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action.
Drawings
The Drawings submitted 04/28/2022 are accepted.
Claim Rejections- 35 USC § 112
The outstanding rejections to the claims are withdrawn in view of the amendments submitted herein. The table has been removed from the claims.
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.
For the following rejections, underlined text indicates newly recited portions necessitated by claim amendment.
Claims 125, 127, 129-135, 140, 142, 144-146, and 150-155 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more. Any newly recited portions are necessitated by claim amendment.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, the claims are directed to method i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03].
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) are as follows:
Independent claim 125:
stratifying the group of subjects into subgroups based on the one or more features;
assigning the subject to one of the subgroups based at least in part on the one or more features;
comparing the expression level of the gene determined in (c) sample component to a reference level of the gene to generate a comparison, wherein the reference level of the gene is obtained from the subgroup to which the subject was assigned one or sample components; and
classifying the subject into a risk group based on one or more digital biomarkers; and
determining an assessment of menstrual health of the subject using the comparison obtained in step g
Dependent claim 129:
wherein step (g) comprises applying a classifier algorithm to generate the comparison
Dependent claim 146:
determining a presence or level of methylation of one or more target genes.
Dependent claim 149:
comparing the expression level of the gene in the fluid sample and the additional fluid sample wherein step (a) is repeated for each of the two or more fluid samples and wherein the level of gene expression for each of the two or more fluid samples are compared in step (c).
Dependent claim 155:
developing a treatment plan for the subject based at least in part on the assessment of menstrual health of the subject determined in (h)
Dependent claims 131-132, 140, and 142, 144-145, and 150-152 recite further steps that limit the judicial exceptions in independent claim 125 and, as such, also are directed to those abstract ideas. For example, claim 131 further limits the menstrual health of claim 125, claim 132 further limits the menstrual cycle disorder of claim 125, claim 140 further limits reference level of claim 125, claim 142 further limit the sample component of claim of 125, claim 143 further limits the gene of claim1 25, claim 144 further limits cells of claim 125, claim 145 further limits the component of claim 125, claims 150-152 further limits the gene of claim 125;
Under the BRI, the instant claims recite judicial exceptions that are an abstract idea of the type that is in the grouping of a “mental process”, such as procedures for evaluating, analyzing or organizing information, and forming judgement or an opinion. The instant claims further recite judicial exceptions that are an abstract idea of the type that is in the grouping of a “mathematical concept”, such as mathematical relationships and mathematical equations.
The claim recites stratifying and assigning. The human mind is capable of stratifying the group of subjects into subgroups based on the one or more features and assigning the subject to one of the subgroups based at least in part on the one or more features. The claims recite mathematical concepts of determining an assessment of menstrual health of the subject using the comparison, determining an assessment of menstrual health of the subject using the comparison obtained in step (g), applying a classifier algorithm to generate the comparison, comparing the expression level of the gene in the fluid sample and the additional fluid, and developing a treatment plan.
Therefore, claim 125 and those claims dependent therefrom recite an abstract idea [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Independent claim 125:
receiving a fluid sample collected from the vaginal cavity of a subject
contacting the fluid sample with a buffer solution under conditions to preserve nucleic acid of the fluid sample;
sequencing the nucleic acid or a complement or a derivative thereof, thereby determining an expression level of a gene of the nucleic acid
obtaining survey data from (i) the subject and (ii) a group of subjects, wherein the survey data comprises one or more features selected from the group consisting of a menstrual cycle phenotype, a physical body characteristic, a disease or condition, a medical treatment, demographic information, lifestyle information, ancestry, sexuality, menstrual management, health care usage, health care access, and health record data relating to the group of subjects
Dependent claim 154:
extracting the nucleic acid from the fluid sample.
Dependent claims 127, 130, 133, 135, 142, 149, 153 recite steps that further limit the recited additional elements in the claims. For example, claims 127, 130, 133, 135, and 149, further limit the fluid sample of claims 125 and claim 153 further limits the sequencing of claim 125;
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to data gathering, such as ”obtaining”, perform functions of collecting the data needed to carry out the judicial exceptions. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
With respect to claim 125, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to receiving a fluid sample, contacting the fluid sample with a buffer solution under conditions to preserve nucleic acid of the fluid sample, extracting the nucleic acid from the fluid sample, and sequencing the nucleic acid or a complement or a derivative thereof, thereby determining an expression level of a gene of the nucleic acid do not impose any meaningful limitations on the abstract idea, or on how the abstract idea is performed. These steps are insignificant extra-solution activity to the judicial exception (MPEP 2106.05(g)(2)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, the courts have found that receiving data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(II)(i)).
As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
With respect to claims 125 and those claims dependent therefrom, the steps of receiving a fluid sample, contacting the fluid sample with a buffer solution under conditions to preserve nucleic acid of the fluid sample, extracting the nucleic acid from the fluid sample, and sequencing the nucleic acid or a complement or a derivative thereof, thereby determining an expression level of a gene of the nucleic acid the courts have recognized the following laboratory techniques as well-understood, routine, conventional activities in the life science arts when they are claimed in a merely generic manner or as insignificant extra-solution activity: i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). The specification further discloses genes expressed in a sample of fluid from the vaginal cavity, such as menstrual fluid, is measured using an acceptable method [0092].
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, the instant claims are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
Response to Applicant Arguments
1. Applicant submits sequencing the nucleic acid or a complement or a derivative thereof, thereby determining an expression level of a gene of the nucleic acid." A user cannot manually compare, classify, and determine gene expression from a fluid sample obtained from a vaginal cavity of a subject. Such a limitation is far too complex to be practically performed within the human mind. MPEP § 2106.04(a)(2)(11l)(A) [p. 7, par. 1].
It is respectfully found not persuasive. The additional element of sequencing is insignificant extra-solution activity to the judicial exception (MPEP 2106.05(g)(2)) and does not integrate the JE into a practical application. The steps of comparing is a mathematical concept and the limitation of classify is also mathematical and can be performed mentally. As these limitations are directed to mathematical concepts and mental activity they are abstract ideas.
2. Applicant submits in addition to the recited sequencing step discussed above, amended claim 125 further recites additional elements that integrate the judicial exception into a practical application such as obtaining survey data, comparing the expression level of the gene determined in ( c) to a reference level of the gene to generate a comparison …and determining an assessment of menstrual health of the subject using the comparison obtained in step (g) [p. 7, par 4-5].
It is respectfully found not persuasive. The additional element of sequencing and obtaining survey data are considered data gathering steps which are insignificant extra-solution activity to the judicial exception (MPEP 2106.05(g)(2)) and does not integrate the JE into a practical application. The steps of comparing is a mathematical concept and the limitation of classify is also mathematical and can be performed mentally. As these limitations are directed to mathematical concepts and mental activity they are abstract ideas.
3. Applicant submits Claim 125 is directed to an improvement to the technical field of assessing menstrual health [p. 7, par. 6].
It is respectfully found not persuasive. It is important to keep in mind that an improvement in the abstract idea itself (e.g. a recited fundamental economic concept) is not an improvement in technology. Furthermore, it is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements or by the additional element(s) in combination with the recited judicial exception. See MPEP 2106.05(a).
4. Applicant submits amended claim 125 describes obtaining survey data comprising "one or more features selected from the group consisting of a menstrual cycle phenotype, a physical body characteristic, a disease or condition, a medical treatment, demographic information, lifestyle information, ancestry, sexuality, menstrual management, health care usage, health care access, and health record data" to stratify subjects into subgroups and determining an assessment of menstrual health of a subject by comparing a subject's expression level of a gene to a reference level of a gene associated with a subgroup. As such, the claimed methods constitute an inventive concept that render the claims significantly more than the judicial exception [p. 8, par. 2].
It is respectfully found not persuasive. The limitation of obtaining data from a survey is a data gathering step which is insignificant extra-solution. The plain meaning of a survey data is labels or values that meet certain features and thus they are met by medical electronic health record or tabular data Obtained that are necessary to carry out the JE.
Claim Rejections - 35 USC § 102
The previous 102 rejections have been withdrawn in view of the claim amendments. The prior art of record does not provide the complete collection stratification assignment and matched reference sequences of steps D through G.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
For the following rejections, instantly claimed elements which are considered to be equivalent to the prior art teachings are described in bold for all claims, and underlined text indicates newly recited portions necessitated by claim amendment.
A. Claims 125, 127, 129-135, 140, 142, 144-146, and 150-155 are rejected under 35 U.S.C. 103 as being unpatentable over Tariyal et al. (WO 2017/180909, published 10/19/2017, cited on IDS dated 07/15/2022, cited on IDS dated 07/15/2022) in view of Giudice et al. (WO2015/050875 A1, published 04/09/2015, newly cited). The instant rejection is newly stated and is necessitated by claim amendment.
Claim 125 is directed to a method of producing a desired preparation for assessment of menstrual health, comprising:
Tariyal discloses preparing A vaginal fluid sample for expression based assessment of endometriosis corresponding to the claimed assessment of menstrual health[00426-00427]
(a) receiving a fluid sample collected from the vaginal cavity of a subject,
Tariyal discloses receiving a used tampon removed from the vaginal canal and releasing its absorbed fluid into a sample receptacle [00327].
(b) contacting the fluid sample with a buffer solution under conditions to preserve nucleic acid of the fluid sample;
Tariyal discloses contacting the collected sample with buffer [00327], RNA collection tubes [00328], and preservation buffers and reagents [00329]. These passages support selecting an RNA preserving preparation for subsequent analysis.
(c) sequencing the nucleic acid or a complement or a derivative thereof, thereby determining an expression level of a gene of the nucleic acid
Tariyal discloses determining biomarker expression by deep sequencing [00426] and identifies RNA sequencing cervical vaginal samples [00450].
(d) obtaining survey data from (i) the subject and (ii) a group of subjects, wherein the survey data comprises one or more features selected from the group consisting of a menstrual cycle phenotype, a physical body characteristic, a disease or condition, a medical treatment, demographic information, lifestyle information, ancestry, sexuality, menstrual management, health care usage, health care access, and health record data relating to the group of subjects;
Tariyal does not disclose the complete survey data collection stratification subject assignment and subgroup workflow of steps D through G.
However, Giudice discloses reviewing subjects cooperative and pathology reports and determining menstrual cycle phase [0125], under the BRI of survey, this collection of subject specific clinical information supports the survey data requirement.
(e) stratifying the group of subjects into subgroups based on the one or more features;
Giudice discloses cross-classification of samples by phase and group label [0126].
(f) assigning the subject to one of the subgroups based at least in part on the one or more features;
Giudice discloses assigning cycle phase through histological assessment and confirmatory methods [0125]. Applying that assignment to the tested subject would identify the corresponding phase subgroup.
(g) comparing the expression level of the gene determined in (c) to a reference level of the gene to generate a comparison, wherein the reference level of the gene is obtained from the subgroup to which the subject was assigned; and
Giudice discloses a population reference matched to the test sample's menstrual cycle phase [0027].
(h) determining an assessment of menstrual health of the subject using the comparison obtained in step (g)
Giudice discloses Comparing the expression level with the expression level of at least one set of genes can a tissue sample from a controlled subject not having endometriosis [claim 19].
Claim 127 is directed to the method of claim 125, wherein the nucleic acid is selected from the group consisting of DNA, RNA or any combination thereof.
Tariyal discloses DNA/RNA embodiments [00328-00329, 00450].
Claim 129 is directed to the method of claim 125, wherein step (g) comprises applying a classifier algorithm to generate the comparison.
Tariyal discloses methods and systems of the present disclosure can be implemented by way of one or more algorithms [00463]. Tariyal further discloses comparing biomarkers at different times using different samples of cervicovaginal fluid (longitudinal menstrual samples) to identify differences or changes in levels of biomarkers [0025 and 0466]. Tariyal also discloses the expression level of the biomarker in the endometriosis sample from a subject diagnosed of endometriosis can be increased or decreased when compared to the expression level of the biomarker in a sample from a second subject that is not diagnosed with endometriosis [00425]. Tariyal does not disclose a classifier algorithm to generate the comparison.
However, Giudice discloses a margin tree classifier [0060] for the match expression comparison of claim 19.
Claim 130 is directed to the method of claim 125, wherein the fluid sample comprises menstrual fluid.
Tariyal discloses the devices and systems disclosed herein can be used for collecting biological samples, such as vaginal fluid, cells, and/or menstrual fluid, for analysis of vaginal microbiomes [00552].
Claim 131 is directed to the method of claim 125, wherein the assessment of menstrual health indicates that the subject has a menstrual cycle disorder.
Tariyal discloses patients with endometriosis mainly complain of pelvic pain, dysmenorrhea, and/or dyspareunia [00424]. Tariyal further discloses the associated symptoms can impact the patient's general physical, mental, and/or social well-being [00424].
Claim 132 is directed to the method of claim 131, wherein the menstrual cycle disorder is heavy menstrual bleeding (HMB).
Tariyal discloses in a randomly selected group of premenopausal women, the most common amount of menstrual flow (measured in a laboratory from all collected tampons and pads) is about two tablespoons (30 mL) in a whole period (www.cemcor.ubc.ca/resources/very-heavy-menstrual-flow) [00419]. Tariyal further discloses the menstrual flow comprises more than just blood [00419]. Tariyal also discloses often, shed cells from the lining of the uterus and endometriosis, secreted mucus, and cervicovaginal fluid (CVF) in the cervicovaginal canal are discharged along with the menstrual blood, which can be collected for diagnostic and/or screening test for diseases [00419].
Claim 133 is directed to the method of claim 125, wherein the fluid sample is obtained from the subject during the subject's menstrual window.
Tariyal discloses detecting changes in expression level of biomarkers [00272], testing biological samples collected from a particular menstrual phase [00272] and assaying at different times (i.e. a longitudinal menstrual sample).
Claim 134 is directed to the method of claim 125, further comprising repeating steps (a)- (h) for two or more longitudinal samples from the subject.
Tariyal discloses detecting changes in expression level of biomarkers [00272], testing biological samples collected from a particular menstrual phase [00272] and assaying at different times (i.e. a longitudinal menstrual sample).
Claim 135 is directed to the method of claim 125, wherein the fluid sample is received in a sample collector selected from the group consisting of a pad, a tampon, a vaginal cup, a cervical cap, a menstrual disk, a cervical disk, a sponge, and an interlabial pad.
Tariyal discloses in some embodiments, the sample collector comprises a cup, a rod, a cylinder, a pad, or a threaded matrix [0021].
Claim 140 is directed to the method of claim 125, wherein the reference level is obtained from a sample of a healthy control subject or an average level from a group of healthy control subjects.
Tariyal discloses comparing biomarkers at different times using different samples of cervicovaginal fluid (longitudinal menstrual samples) to identify differences or changes in levels of biomarkers [0025 and 0466]. Tariyal further discloses the expression level of the biomarker in the endometriosis sample from a subject diagnosed of endometriosis can be increased or decreased when compared to the expression level of the biomarker in a sample from a second subject that is not diagnosed with endometriosis [00425]. Giudice also discloses healthy subjects sample or population reference [0027].
Claim 142 is directed to the method of claim 125, wherein the nucleic acid for step (c) comprises RNA.
Tariyal discloses nucleic acid samples (biological material) that include RNA and DNA [00231]. Giudice also discloses mRNA expression analysis [00253].
Claim 144 is directed to the method of claim 125, wherein the fluid sample comprises of one or more types of cells selected from the group consisting of endothelial cells, epithelial cells, mesenchymal cells, erythrocytes, stromal cells, immune cells, and stem cells.
Tariyal discloses red blood cells in the extracted sample [00253]. Erythrocytes are also listed as an alternative.
Claim 145 is directed to the method of claim 125, wherein the nucleic acid is miRNA.
Tariyal discloses many miRNA in table 13.
Claim 146 is directed to the method of claim 125, wherein the method further comprises determining the presence or level of methylation of one or more target genes.
Tariyal discloses detection of endometriosis is achieved by detecting differential expression of methylation biomarkers [00436].
Claim 150 is directed to the method of claim 125, wherein the gene is selected from the group consisting of ABLIMI, ALAS2, APP, C18orf25, CAPZA1, CCL2, CCL3, CCL4, CLECl2A, CLEC4E, DENND4A, DPYSL2, FAU, FBXO32, GYPC, HBA1, HBA2, HBB, HIFlA, HTRA1, IL18, ILlA, IL7R, LAMB1, LAMC1, LOXL2, MMP14, MMP2, PLOD1, PSMD2, PTBP3, RBM38, RPLP1, RPS9, SASH1, SDCBP, SEC61A1, SIK1, SLC25A39, SND1, SORT1, TBX3, TMBIM6, TNFSF15, TRIM58, UBA52, VNN1, and ZNF426.
Tariyal discloses CCL2 in table 10.
Claim 151 is directed to the method of claim 125, wherein the gene is selected from the group consisting of ADAMTS2, ADAMTS4, ANKRD12, ANTXR1, ASPH, CDYL, CLU, GREM1, IGF2, LGALS3, MAN1A2, MMP3, MPZL2, NT5E, PAMR1, RNF11, S100A14, SEMA3C, SERPING1, SLPI, ST 14, TGFA, and TRIP 12.
Tariyal discloses ASPH in table 10.
Claim 152 is directed to the method of claim 125, wherein the gene is selected from the group consisting of ACE, BSG, CD151, CD160, CD34, CD36, CD44, CD47, CD80, CD86, CD93, CDH1, CDH2, CDH5, COL4A1, COL4A2, CXCL16, EMCN, ENG, ENTPD1, EPCAM, ESAM, F3, F8RA, FN1, ICAM1,IL13RA1, ILiR1, ITGB3, JAM2, KDR, KIT, KLF4, MCAM, NECTIN2, NOTCHI, PECAMI, PROCR, PTPRC, SDC1, SELE, SELP, SPP1, THBD, VCAM1, VWF, and CD248
Tariyal discloses ICAM1 in table 10.
Claim 153 is directed to the method of claim 125, wherein prior to (c), the nucleic acid is preserved for at least 1 day.
Tariyal discloses the storage device can store and preserve the sample and absorbed fluids for at least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 15 days, 30 days, 2 months, 3 months, 6 months, 12 months, 2 years, 5 years, 10 years, or longer [00310].
Claim 154 is directed to the method of claim 125, wherein prior to (c), the method further comprises extracting the nucleic acid from the fluid sample.
Tariyal discloses DNA/RNA extraction reagents [00329].
Claim 155 is directed to the method of claim 125, further comprising developing a treatment plan for the subject based at least in part on the assessment of menstrual health of the subject determined in (h).
Tariyal does not disclose developing a treatment plan.
However, Giudice discloses treatment assigned or provided based on the diagnosis [claim 9].
In regard to claim(s) 125, 127, 129-135, 140, 142, 144-146, and 150-155, It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Tariyal’s preparation and sequencing method with Giudice’s clinical data grouping and phase matched reference comparison to account for cycle phase differences when interpreting expression for menstrual health assessment. A reasonable expectation of success is proposed for implementing this phase match comparison because Tariyal already applies endometrial expression analysis to its collected materials and points to Giudice’s diagnostic approach.
B. Claim 149 are rejected under 35 U.S.C. 103 as being unpatentable over Tariyal in view of Giudice, as applied to claims 125, 127, 129-135, 140, 142, 144-146, and 150-155as above, and in further view of Bexon et al. (Bexon, Kimberley, and Graham Williams. "Characterising the fluctuation of microRNA expression throughout a full menstrual cycle." Forensic Science International: Genetics Supplement Series 5 (2015), newly cited).
Claim 149 is directed to the method of claim 125, wherein the method further comprises obtaining an additional fluid samples from the vaginal cavity of the same subject, wherein the fluid sample and the additional fluid sample are from different time points within the subject's menstrual cycle, and wherein the method further comprises comparing the expression level of the gene in the fluid sample and the additional fluid sample wherein step (a) is repeated for each of the two or more fluid samples and wherein the level of gene expression for each of the two or more fluid samples are compared in step (c).
Tariyal discloses vaginal sample collection and preservation [00327- 00329] expression analysis by deep sequencing [00426] and RNA sequencing [00450] and further identifying micro RNA expression biomarkers for assessing endometriosis [00438]. Tariyal and Giudice do not disclose the comparison between samples collected from the same subject at different time points within the same menstrual cycle.
However, Bexon discloses collecting low vaginal swabs daily from 5 individuals over a period of 31 days [abstract]. This supports the repeated collection of vaginal material from the same subject including different collection days within an individual menstrual cycle. Bexon further discloses determining mRNA expression using stem loop reverse transcription followed by quantitative PCR [abstract]. This reads on determining and comparing expressions of the same marker and samples collected at different types.
In regard to claim 149 it would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the method of material in Giudice by obtaining an additional vaginal fluid sample from the same subject at another time within the menstrual cycle determining expression of the same selected gene and comparing its expression between the samples the motivation would have been to evaluate temporal variation in biomarker expression when interpreting the menstrual health assessment vaccine discloses expression variability across sampling days where Tariyal disclosed regularly monitoring a subject's health condition. One would have had reasonable expectation of obtaining comparable measurements by applying the same sample preparation expression assay to both samples.
Conclusion
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.
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/D.M.B./Examiner, Art Unit 1685 /Soren Harward/Primary Examiner, TC 1600
