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 .
Priority
This application 17/772,829 filed on 04/28/2022 is a 371 national phase of PCT/US2020/058406 filed on 10/30/2020 and claims the benefit of provisional U.S. Patent Application No. 62/929,579, filed on 11/01/2019; provisional U.S. Patent Application No. 62/930,465, filed on 11/04/2019; and provisional U.S. Patent Application No. 63/061,709, filed on 08/05/2020.
The priority date of claim 113 and its dependent claims is thus determined to be 11/01/2019, the filing date of provisional U.S. Patent Application No. 62/929,579.
Status of Claims
Applicant’s amendments to claims filed 07/01/2026 in response to the Non-Final Rejection mailed 04/02/2026 are acknowledged.
Claims 113, 117-120, 123, 124, 126, 128, and 130 are amended.
Claim 125 has been canceled.
Claims 113, 117-120, 123, 124, 126-128, 130-134, and 136-137 are pending and under examination.
Response to Remarks filed 07/01/2026
The amendments and arguments presented in the papers filed 07/01/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 04/02/2026 listed below have been reconsidered as indicated.
a) The 35 USC 112(b) indefiniteness rejections of claims 113,117-120,123-128,130-134,136, and 137 have been withdrawn in view of the amendments to claims and the cancellation of claim 125.
b) The rejection of claims 113,117-120,123-128,130-134,136, and 137 under 35 U.S.C. 103 have been modified in view of the amendments to claims and the cancellation of claim 125.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
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 113, 117-120, 123-124, 126-128, 130-134, and 136-137 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.
Regarding claim 113, it is not clear how the recited preamble is intended to breathe life and meaning into the claim. The preamble of the claim recites “a method for preparation of a menstrualome fingerprint to identify a health state of a subject”. However, the recited active method steps in the claim only require “(g) constructing a sample menstrualome fingerprint from the menstrualome biomarkers, wherein the menstrualome fingerprint comprises a level or presence of the menstrualome biomarkers in the cervicovaginal or menstrual fluid sample”. Thus steps (a) to (g) result in the construction (i.e. preparing) of a menstrualome fingerprint without any required identification of a health state. Claim 113 further recites the limitation “(h) comparing the sample menstrualome fingerprint to a reference menstrualome fingerprint, wherein the reference menstrualome fingerprint comprises a level or presence of the menstrualome biomarkers associated with the health state.” The “reference menstrualome fingerprint” thus comprises “---menstrualome biomarkers associated with the health state” and is not prepared by active steps (a) – (g) recited in the claim. Thus, it is unclear what relationship exists between the active steps preparing a menstrualome fingerprint and identifying a health state, or if the method is intended to somehow require more to accomplish the goal set forth in the preamble. If it is the latter, then it appears that the claims are incomplete, as they fail to provide any active steps that clearly accomplish the goal of “preparation of a menstrualome fingerprint to identify a health state of a subject” set forth by the preamble of the claim.
Claims 117-120, 123-124, 126-128, 130-134, and 136-137 are similarly indefinite because they directly or indirectly depend from claim 113.
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 113,117-120,123, 124, 126-128,130-134,136, and 137 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
These are new rejections necessitated by claim amendments.
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.
Step 1
The claimed invention is directed to the statutory category of a process.
Step 2A, Prong One
The claim is (claims are) taken to be directed to an abstract idea, a judicial exception.
Claim 113 is directed to a method comprising “(h) comparing the sample menstrualome fingerprint to a reference menstrualome fingerprint ---”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the comparing step encompasses the mental step of looking at two sets of menstrualome fingerprint and making mental judgements.
Claims 117-120, 123, 124, 126-128, 130-134, and 136-137 depend from claim 113 , and require the same step of “selecting a plurality of the menstrualome biomarkers”.
Claim 130 is directed to a method comprising “wherein the plurality of menstrualome biomarkers is selected to comprise biomarkers that display differential presence or level in cervicovaginal or menstrual fluid between two or more health states of the subject”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the selecting step encompasses the mental step of looking at menstrualome biomarkers, making mental judgements, and choosing a subset.
Step 2A, Prong Two
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 claim 113 additionally recites the active steps ” a) obtaining a cervicovaginal or menstrual fluid sample from a subject -- ; (b) eluting the cervicovaginal or menstrual fluid sample---; (c) sequencing at least a portion of the RNA molecules of the cervicovaginal or menstrual fluid sample --; (d) obtaining a whole blood sample from the subject ---; (e) sequencing at least a portion of the additional RNA molecules of the whole blood sample---; (f) comparing the RNA sequences of the cervicovaginal or menstrual fluid sample and the RNA sequences from the whole blood sample by performing a clustering analysis — ; (g) construct[ing] a sample menstrualome fingerprint”, these are not integrations of the exception into a practical application. Instead, these elements are data gathering and data analysis required to perform the method.
Additional claims recite limitations on collection time points and sample sources (claims 117-120, 123, 124 and 131-134) or repeat the data gathering and analysis steps of claim 113 (claim 126 and 130). These are not integrations of the exception into a practical application. Instead, claims 117-120, 123-124 present general parameters for performing the method while claims 126 and 130 repeat steps of claim 1 that are data gathering and data analysis required to perform the method.
Lastly, claim 137 recites the limitation “wherein the clustering analysis comprises a k means clustering, a heat map, a tSNE dimensionality analysis, or a principal component analysis”. This is not an integration of the exception into a practical application. Instead, these elements are routine and conventional data analysis steps required to perform the method.
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to obtaining samples, eluting material, obtaining RNA sequences, and performing cluster analysis are techniques that are routine, conventional, and well-known in the art as demonstrated in the 103 rejection documented below.
Furthermore, 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);
For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claims 113,117-120,123-124, 126-128,130-134,136, and 137 are/remain rejected under 35 U.S.C. 103 as being unpatentable over Tariyal et al. (WO 2017/180909, on IDS dated 07/15/2022) in view of Hanson et al. (Messenger RNA biomarker signatures for forensic body fluid identification revealed by targeted RNA sequencing. 2018 Forensic Science International: Genetics 34:206-221, on IDS dated 12/13/2023).
This maintained rejection has been modified to address claim amendments filed on 07/01/2026.
Regarding claim 113, Tariyal teaches devices and methods for analysis of vaginal biological samples (abstract) for detecting and monitoring health conditions (para 12).
Regarding step (a), Tariyal teaches a sample collector comprising an absorbent-diffuse material that can absorb cervicovaginal or other vaginal fluids (i.e. menstrual fluid) (paras 54, 254). Tariyal teaches collecting a vaginal biological sample from a subject for monitoring of a health condition (para 59). Tariyal further teaches a biological sample comprises RNA (paras 231-233).
Regarding step (b), Tariyal teaches eluting the biological material and receiving the biological sample with buffer from the sample collector (para 416, step 12).
Regarding step (c), Tariyal teaches extracting RNA from the vaginal biological sample, (paras 151 and claim 60) and sequencing the RNA (para 487), thereby obtaining RNA sequences from the vaginal biological sample.
Regarding step (d), Tariyal teaches whole blood as a biological sample (paras 232 and 418) and extracting RNA (para 151 and claim 60) and sequencing (paras 18, 89, 446, 450) to obtain RNA sequences from the biological sample, as encompassed by step (d).
Regarding step (e), Tariyal teaches detecting a presence or level of biomarkers in a sample (para 25) and comparing biomarker expression level of the biomarker to a sample from the subject that is in a different region of the body (e.g. a whole blood sample which is taught as a biological sample) (para 425).
Regarding step (f), Tariyal teaches that 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 the subject that is in a different region of the body other than the reproductive system (para 425), i.e. whole blood. Tariyal also states that biomarkers found in cervicovaginal fluid can be expected to show more specificity and sensitivity for gynecopathological conditions as compared to circulating blood (i.e. whole blood) (para 444).
However, Tariyal does not teach verbatim comparing the RNA sequences of the vaginal biological sample to whole blood.
Tariyal also does not teach regarding step (f): comparing the RNA sequences of the cervicovaginal or menstrual fluid sample and the additional RNA sequences from the whole blood sample by performing a clustering analysis to identify one or more clusters of RNA sequences hat display differential presence or level in cervicovaginal or menstrual fluid as compared to whole blood, wherein the one or more clusters of RNA sequences that display differential presence or level in cervicovaginal or menstrual fluid as compared to whole blood are identified as menstrualome biomarkers.
Hanson teaches a method identifying RNA biomarker signatures in different body fluids, the method comprising obtaining RNA sequences using an absorbent collector from multiple sources including vaginal secretions, menstrual blood and blood (methods, p. 207, col. 2), and performing clustering analysis (p. 209 col. 1-2 and Fig. 1) to identify groups (i.e. clusters) of RNA sequences displaying different levels in vaginal samples compared to blood (Fig. 1, Table 2). Hanson teaches identifying sequences with differential level or presence in vaginal secretions compared to blood (Fig. 1), thus satisfying the requirement of identifying clusters of RNA sequences that display differential presence or level in cervicovaginal or menstrual fluid as compared to whole blood as menstrualome biomarkers. Hanson teaches that different body fluid classes show clear and distinct intra-class differences in gene expression, while samples of the same body fluid/tissue type cluster together (p. 213, col. 2).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Tariyal and Hanson to arrive at the instantly claimed invention. The modification would have entailed obtaining the RNA sequences of cervicovaginal fluid and whole blood samples using the methods taught by Tariyal. The modification would have further entailed comparing the RNA sequences of cervicovaginal fluid and whole blood using the techniques of Hanson to identify markers specific to cervicovaginal (or menstrual) fluid. Tariyal teaches methods for extracting RNA and sequencing RNA from biological samples in order to obtain RNA sequences for the biological samples and states that biomarkers in cervicovaginal fluid are expected to have more sensitivity and specificity for gynecopathological conditions as compared to circulating blood. One would have been motivated to identify sequences in both cervicovaginal fluid and whole blood samples by the expectation that markers found in cervicovaginal fluid and not whole blood would be more specific and sensitive (as stated by Tariyal, para 444). One would have further been motivated to use the methods of Hanson to characterize differences between cervicovaginal or menstrual fluid and whole blood in order to expand the number of identified cervicovaginal fluid markers for use a menstrualome biomarkers to provide better insight into gynecological health conditions. Hanson teaches clustering groups markers by sample type. One of skill in the art would have recognized that these comparison and analysis tools could be used to identify markers differentially expressed between fluid samples in any context. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding step (g), Hanson teaches clusters of RNA sequences that display differential presence or level in cervicovaginal or menstrual fluid as compared to whole blood (menstrualome biomarkers) (Fig. 1) and reports the differential level or presence of the menstrualome biomarkers in the cervicovaginal or menstrual fluid (Fig. 1 and Table 2), which reads on constructing a menstrualome fingerprint comprising the level or presence of the menstrualome biomarkers in the cervicovaginal or menstrual fluid.
Regarding step (h), Tariyal teaches biomarkers with differences in expression level (para 425) such as those listed in Tables 2-10 can be used for determining the presence or absence of endometriosis or other pathology in a biological sample, which reads on a reference menstrualome fingerprint, wherein the reference menstrualome fingerprint comprises biomarkers that are associated with a health state.
Regarding claim 117, Tariyal teaches assaying at different times (para 466) and using the method for monitoring effectiveness of a medical or therapeutic regimen (para 270), as encompassed by the claimed prior time point before a medical treatment and the first sample time point after the medical treatment.
Regarding claim 118, Tariyal teaches assaying a condition at different times (para 466) and using the method for monitoring effectiveness of a medical or therapeutic regimen (para 270).Tariyal further teaches surgical procedures are a medical treatment (para 485). Thus, the teachings of Tariyal are encompassed by a prior time point before a surgery and a sample collected at a time point after the surgery.
Regarding claim 119, Tariyal teaches a change of expression level of the biomarker indicates a pathological condition associated with endometriosis (para 25), a menstrual disorder.
Regarding claim 120, Tariyal teaches a change of expression level of the biomarker indicates a pathological condition associated with endometriosis (para 25).
Regarding claim 123, Tariyal teaches the sample may be from a subject diagnosed with a disease (health state) (paras 230, 270). Tariyal teaches that the biomarker expression level of a subject diagnosed with endometriosis can be compared to the expression level of the biomarker in a sample from a second subject that is not diagnosed (para 425), which is encompassed by comparing a sample menstrualome fingerprint to a reference menstrualome fingerprint comprising a level or presence of the plurality of menstrualome biomarkers from a reference group of subjects with the health condition.
Regarding claim 124, Tariyal teaches that the biomarker expression level of a subject diagnosed with endometriosis can be compared to the expression level of the biomarker in a sample from a second subject that is not diagnosed, or to a sample from the subject that is in a different region of the body (i.e. a reference fingerprint) (para 425).Tariyal teaches the method further comprises monitoring the health condition regularly, including monitoring the health condition about every 10 to 90 days, as encompassed by the claimed limitation of comparing a sample to a prior time point (para 33).
Regarding claim 126, regarding step (a) Tariyal teaches monitoring a health condition about every 10 to 90 days (para 33) and also self-monitoring on a regular basis (para 270), i.e. obtaining a second sample from a subject. Tariyal teaches a sample collector comprising an absorbent-diffuse material that can absorb cervicovaginal or other vaginal fluids (i.e. menstrual fluid) (paras 54, 254). Tariyal teaches collecting a vaginal biological sample from a subject for monitoring of a health condition (para 59). Tariyal further teaches a biological sample comprises RNA (paras 231-233).
Regarding step (b), Tariyal teaches eluting biological material and receiving the biological sample with buffer from the sample collector (para 416, step 12).
Regarding step (c), Tariyal teaches extracting RNA (para 151 and claim 60) and sequencing the RNA (para 487), which reads on sequencing RNA and obtaining RNA sequences from an additional cervicovaginal or menstrual fluid sample.
Regarding step (d), Tariyal teaches detecting a presence or level of biomarkers in the sample, i.e. cervicovaginal fluids or menstrual blood (menstrual fluid) (para 25), which reads on constructing an additional menstrualome fingerprint that comprises a level or presence of the menstrualome biomarkers from the additional cervicovaginal or menstrual fluid sample.
Regarding claim 127, Tariyal teaches using the method for self-monitoring on a regular basis including about every month, or about every 28-40 days, and that the self-monitoring period can be synchronized with a woman's menstrual cycle (para 270), i.e. samples from the same subject. Thus, Tariyal teaches elements encompassed by samples collected from separate menstrual cycles.
Regarding claim 128, Tariyal teaches using the method to detect changes of biomarker expression levels to indicate a pathological condition (paras 25 and 272) or monitor a subject’s health status (para 12). Tariyal further teaches monitoring a health condition regularly (para 33). This monitoring of changes in biomarkers from samples collected regularly satisfies the requirement of the claimed third menstrualome fingerprint obtained by comparing biomarkers between a first and second sample from the subject.
Regarding claim 130, Tariyal teaches biomarkers indicative of a pathological condition determined by changes in expression level of biomarkers in samples collected at different times in the menstrual cycle (para 25).
Regarding claim 131, Tariyal teaches using the method for monitoring effectiveness of a medical or therapeutic regimen (para 269), encompassing the before and after medical treatment of claim 117.
Regarding claim 132, Tariyal teaches using the method for self-monitoring of effectiveness of a medical regimen (para 270), as encompassed by the claimed before and after surgery.
Regarding claim 133, Tariyal teaches a change of expression level of the biomarker indicates a pathological condition associated with endometriosis (para 25), a menstrual disorder.
Regarding claim 134, Tariyal teaches a change of expression level of the biomarker indicates a pathological condition associated with endometriosis (para 25).
Regarding claim 136, Tariyal teaches monitoring the health condition regularly, including monitoring the health condition about every 10 to 90 days (para 33) including during menstrual phase (MP), proliferative phase (PE), early secretory phase (ESE), mid-secretory phase (MSE) (para 425), i.e. different days in the menstrual cycle.
Regarding claim 137, Tariyal does not teach any of the claimed methods of clustering analysis.
Hanson teaches clustering analysis with a heat map (Fig. 1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Tariyal and Hanson to arrive at the instantly claimed invention. The modification would have entailed using the clustering analysis of Hanson with the method of Tariyal to construct a menstrualome fingerprint comprising a level or presence of the menstrualome biomarkers, i.e. markers differentially expressed in cervicovaginal or menstrual fluid samples compared to whole blood. One would have been motivated by the ability to resolve differences in level or expression of RNA biomarkers in vaginal samples (cervicovaginal or menstrual) compared to a control sample of whole blood. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Response to Arguments against Claim Rejection - 35 U.S. C § 103
The response asserts that Tariyal does not describe a method for comparing cervicovaginal and menstrual fluid to whole blood. Instead, Tariyal cites whole blood as one possible biological sample to be analyzed. While whole blood is mentioned as a sample, it is never compared to a sample comprising cervicovaginal or menstrual
fluid as is presently claimed. (p. 9-10)
Applicant's arguments have been fully considered but are not persuasive.
Tariyal teaches whole blood as a biological sample for use and further teaches methods comprising obtaining RNA sequences from biological samples and using RNA expression levels to determine health states. Tariyal further teaches comparing expression levels in cervicovaginal samples to samples found in other part of the body. As stated in the maintained and updated 103 rejection above, Tariyal further specifically states that biomarkers found in cervicovaginal fluid are expected to show more specificity and sensitivity for gynecopathological conditions as compared to circulating blood. Thus, one of skill in the art would have been motivated to select whole blood as the non-vaginal sample for comparison in order to identify biomarkers specific to the cervicovaginal sample.
The response further asserts that Tariyal does not teach "performing a clustering analysis to identify one or more clusters of RNA sequences that display differential presence or level in cervicovaginal or menstrual fluid as compared to whole blood." (p. 10).
Applicant's arguments have been fully considered but are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the clustering analysis of RNA sequences is taught by Hanson. One of skill in the art would have recognized the benefit of using the clustering analysis of Hanson on the samples of Tariyal, as Hanson demonstrates the ability of the method to identify markers differentially expressed in cervicovaginal fluid as compared to whole blood. A difference that Tariyal states is expected to be beneficial for characterizing gynecopathological conditions, i.e. health states.
The response asserts that Hanson is directed to the identification of menstrual blood samples for forensic use. The purpose of Hanson is merely to identify the source of a biological fluid for purposes of a criminal investigation, not to determine markers associated with a health state in the subject. Hanson optimizes for identifying markers that would strongly associate with tissue type, rather than identifying markers that are associated with a health state. (p. 10)
Applicant's arguments have been fully considered but are not persuasive.
As presented in the 103 rejection above, Hanson teaches differential level or presence of markers in cervicovaginal fluid compared to whole blood samples. The instant claim requires a menstrualome fingerprint comprising a level or presence of the menstrualome biomarkers in the cervicovaginal or menstrual fluid sample, where menstrualome biomarkers are solely required to comprise clusters of RNA sequences that display differential presence or level in cervicovaginal, or menstrual fluid as compared to whole blood. Thus, the clustering and reported level of markers differentially expressed in cervicovaginal samples versus whole blood by Hanson satisfy the requirements of menstrualome biomarkers and a menstrualome fingerprint comprising those menstrualome biomarkers. The claim as written does not require the sequencing and clustering analysis identify markers associated with a health state, only the identification or markers specific to cervicovaginal or menstrual fluid compared to whole blood, which Hanson provides the method for. Furthermore, the limitation of a “health state” encompasses all possible health states including but not limited to a healthy normal state or even a mental state.
The response asserts that there is a notable difference between biomarkers detected in whole blood and biomarkers that are unique to menstrual and cervicovaginal fluid. The response further asserts that menstrual fluid is a combination of distinct components and that it was surprising and unexpected that each component within menstrual blood would have very distinct and separable gene expression patterns. The response asserts that arriving at the claimed solution would require more than conventional technical means because it was unexpected that the components analyzed would have distinct patterns as compared to peripheral blood. (p. 10)
Applicant's arguments have been fully considered but are not persuasive. ‘
As recited in the 103 rejection above, Tariyal teaches that biomarkers found in cervicovaginal fluid would be expected to show more specificity and sensitivity for gynecopathological conditions as compared to circulating blood. Furthermore, Hanson teaches that clustering of RNA sequences identifies differences in marker expression between cervicovaginal fluid and whole blood samples.
The response asserts that the components identified by Hanson show significant overlap between menstrual blood, peripheral blood, and cervicovaginal samples (see Hanson at p. 211, "All four vaginal secretion biomarkers and all six blood biomarkers were also expressed in the menstrual blood samples ... "). (p. 11)
Applicant's arguments have been fully considered but are not persuasive.
While Hanson could identify biomarkers common to more than one tissue/sample type, as recited above in the 103 rejection, Hanson teaches clusters and groups of markers differentially expressed in cervicovaginal and menstrual fluid compared to whole blood. Furthermore, the instant claims are directed to biomarkers with differential levels of expression, which encompasses markers expressed in both samples but at different levels of expression.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 113,117-120, 123-124, 126-128,130-134 and 136-137 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,446,011 in view of Tariyal et al. (WO2017/180909, on IDS dated 07/15/2022) and Hanson et al. (Messenger RNA biomarker signatures for forensic body fluid identification revealed by targeted RNA sequencing. 2018 Forensic Science International: Genetics 34:206-221, on IDS dated 12/13/2023).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims are species claims that anticipate the genus claims of instant application.
Regarding claim 113, claims 1, 6-10, 19, and 20 of the ‘011 patent require collecting a vaginal sample comprising cervicovaginal fluid with a sample collector that is absorbent, removing the sample from the collector and extracting DNA, RNA, or protein (biological material) to detect the presence, absence or change in expression level of a biomarker, and monitoring over 10-90 days (longitudinal menstrual samples). Claims 1 and 9 further requires detecting a presence, absence of change in biomarkers.
Claims of the ‘011 patent do not require obtaining a whole blood sample from the subject, obtaining RNA sequences from the whole blood sample or identifying genes with differential presence or level in cervicovaginal or menstrual fluid as compared to whole blood by performing a clustering analysis.
The teachings of Tariyal and Hanson as they relate to this claim are given previously in this office action and are fully incorporated here.
Regarding claims 117 and 118, the claims of the ‘011 patent require monitoring a health condition (patent claim 1) and collecting samples at different time points (patent claims 9 and 10) but do not require the prior time point comprises before a medical treatment and the first sample comprises a time point after the medical treatment (instant claim 117) or the prior time point comprises before a surgery and the first sample comprises a time point after the surgery (instant claim 118).
The teachings of Tariyal as they relate to these claims are given previously in this office action and are fully incorporated here.
Regarding claim 119, claims 6 and 12 of the ‘011 patent require detecting a presence or absence of a biomarker to test a presence or absence of a health condition, including endometriosis, as encompassed by the claimed menstrual disorder of instant claim 119.
Regarding claim 120, claims 6 and 12 of the ‘011 patent require detecting a presence or absence of a biomarker to test a presence or absence of a health condition, including endometriosis.
Regarding claim 123, claims of the ‘011 do not require a reference menstrualome fingerprint wherein the reference menstrualome fingerprint comprises the level and/or presence of the plurality of menstrualome biomarkers in a reference group of subjects.
The teachings of Tariyal as they relate to these claims are given previously in this office action and are fully incorporated here.
Regarding instant claim 124, claims 12- 15 require a change of expression level of said biomarker is indicative of a disorder or disease, which reads on a level or presence of the plurality of menstrualome biomarkers in the subject at a prior time point to the collection of the cervicovaginal or menstrual fluid sample.
Regarding claim 126, claim 9 of the ‘011 patent requires collecting a second vaginal biological sample and detecting a presence, an absence, or a change in expression level of a biomarker.
Regarding claim 127, claim 10 of the ‘011 patent requires monitoring the biomarker about every 10 days to about every 90 days, as encompassed by the claimed separate menstrual cycles of instant claim 127.
Regarding claim 128, claims 9 and 10 of the ‘011 patent require collecting a second vaginal biological sample and monitoring biomarkers over time, as encompassed by the claimed third menstrualome fingerprint of instant claim 128.
Regarding claim 130, claims 7 and 8 of the ‘011 patent require a biological sample comprised of cervicovaginal fluid.
Regarding claims 131 and 132, claims of the ‘011 patent do not require wherein the two or more health states comprise before and after a medical treatment (instant claim 131); or wherein the two or more health states comprise before and after a surgery (instant claim 132).
The teachings of Tariyal as they relate to these claims are given previously in this office action and are fully incorporated here.
Regarding claim 133, claims 6 and 12 of the ‘011 patent require detecting a presence or absence of a biomarker to test a presence or absence of a health condition, including endometriosis, as encompassed by the claimed menstrual disorder of instant claim 133.
Regarding claim 134, claims 6 and 12 of the ‘011 patent require detecting a presence or absence of a biomarker to test a presence or absence of a health condition, including endometriosis.
Regarding claim 136, claims of the ‘011 patent do not require the second menstrualome fingerprint comprises a time point from a different day within a menstrual cycle of the subject.
The teachings of Tariyal as they relate to this claim is given previously in this office action and are fully incorporated here.
Regarding claim 137, claims of the ‘011 patent do not require a clustering analysis selected from the listed limitations.
The teachings of Tariyal and Hanson as they relate to this claim is given previously in this office action and are fully incorporated here.
Response to Arguments against Double Patenting
Applicant requests the withdrawal of the nonstatutory double patenting rejections on the basis of the asserted deficiencies of Tariyal and Hanson.
Applicant's arguments have been fully considered but are not persuasive.
Asserted deficiencies in the teachings of Tariyal and Henson are addressed in the 103 rejections above and incorporated here in the double patenting rejections
Conclusion
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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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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