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 .
Status of Application/Amendment/Claims
This Office action is in response to the communications filed on October 13, 2025.
Currently, claims 12-13, 16-18, and 21-22 are pending and under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Maintained Objections/Rejections
Priority
The denial of priority benefit to the ‘086 provisional application filing date is maintained for the reasons as set forth in the Office action mailed on July 14, 2025 because applicant did not address the priority denial issues in the remarks filed on October 13, 2025.
Claim Rejections - 35 USC § 112
Claims 12-13, 16-18, and 21-22 remain rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement for the reasons as set forth in the Office action mailed on July 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on October 13, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims as amended to recite non-serum samples comply with the written description requirement because the specification provides data with ovarian theca cells. In response, it is noted that the limitation of “the biological sample is not serum” includes but is not limited to “blood, urine, plasma, or saliva and/or biopsy or surgical specimen of the ovary, endometrium, adipose tissue, or skeletal muscle” as recited in claims 17 and 22. That is, the “ovarian theca cells” in which the expression levels of the instantly recited PCOS diagnostic markers were assessed are not representative of “blood, urine, plasma, or saliva and/or biopsy or surgical specimen of the ovary, endometrium, adipose tissue, or skeletal muscle”.
Applicant argues that the declaration concurrently submitted with the remarks provides evidence of written description support for “the recitation of RNAi composition s as a therapy”. In response, it appears that the “declaration” referred to by applicant appears to mean the declaration filed under 37 CFR §1.132 on October 13, 2025. It is noted that the generic statements in paragraph 3 of the §1.132 declaration such that techniques/methods for making and delivering “any” RNAi compositions for downregulating the recited genes were known are far from providing evidence that “appropriate treatment” for PCOS is provided to a PCOS patient by “a RNAi containing composition” that “decrease the expression of DENND1A.V2 or other PCOS gene products”, in particular the “miRNA or a miRNA mimic” that is administered as the as required in claims 16 and 21. That is, the instant specification does not identify which “miRNA” decreases not only the DENND1A.V2 but also “other” PCOS gene products to a therapeutic level of providing “an appropriate treatment for PCOS” as required by the claims. It is noted that the declarant pointed out Rupiamoole et al. (2017) and paragraphs 0055-0057 of the instant specification. As an initial matter, it is noted that paragraphs 00055-00057 of the specification do not appear to pertain to RNAi compositions, let alone miRNA compositions for downregulating the recited genes, and the paragraphs do not even identify which miRNA has the therapeutic function in the claimed method. Regarding the Rupiamoole reference, it is noted that there is no teaching in Rupiamoole that clearly identifies a miRNA or a miRNA mimic that downregulates PCOS genes and results in the treatment of a PCOS patient when administered. The generic review article pertaining to “miRNA therapeutics” does not even mention PCOS or any of the genes recited in the claims. Hence, the 2017 reference does not provide any evidence or written description support for the RNAi (e.g., miRNA)-mediated treatment method for treating a PCOS patient.
In view of the foregoing, this rejection is maintained.
Claim Rejections - 35 USC § 102
Claims 12-13, 17-18, and 22 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Modi for the reasons as set forth in the Office action mailed on July 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on October 13, 2025 have been fully considered but they are not persuasive. Applicant argues that the declaration concurrently filed with the remarks “demonstrates the novelty” of the claimed subject matter thus Mondi does not teach the rejected claims. It appears applicant refers to the declaration under 37 CFR §1.132 by “the declaration”. In response, it is noted that the declaration under 37 CFR §1.132 filed on October 13, 2025 is insufficient to show that Modi does not describe the subject matter of claims 12-13, 17-18, and 22 for the following reasons:
The declarant states that “the data disclosed in the Modi thesis was known to be unreliable and was actually contradictory to the data disclosed in the present application.” See paragraph 4. In particular, the declarant points out page 51 and states the data in Figure 3.3 are “not significant” thus “it is clear that miR-130b-3p could not be used as a diagnostic for disorders” such as PCOS. In response, applicant’s attention is directed to the fact that the lack of significant correlation disclosed at page 51 pertains to the lack of positive correlation between miR-130b-3p and DENND1A.V2 or DENND1A.V1. It is highly questionable as to how the declarant, “advisor and mentor” (see page ii) of the Modi dissertation can possibly make such an incorrect statement on the record. The Modi dissertation expressly discloses a negative correlation between miR-130b-3p and DENND1A.V2, but not between miR-130b-3p and DENND1A.V1. See page 55 disclosing that miR-130b-3p “showed a trend negative correlation with DENND1A.V2”. Now, note that claim 18 expressly requires that the ratio between DENND1A.V2 mRNA and miR-130b-3p is “higher than the corresponding reference ratio”, thereby requiring a negative correlation between the two biomarkers such that the DENND1A.V2 expression level is high, while the miR-130b-3p expression level is low. Also note that the Modi reference expressly discloses that miR-130b-3p expression is lower in PCOS cell samples compared to normal cell samples (see Figure 3.2(B)), while the mRNA variant of DENND1A.V2 “is increased in PCOS theca cells”. See page 39. Hence, even without the data in Figure 3.3, it is clear that there is a negative correlation between DENND1A.V2 and miR-130b-3p in PCOS cells. That is, contrary to declarant’s statement that Modi’s teachings are “actually contradictory” to what is disclosed in the instant application, the teachings Modi in relation to the increased expression of DENND1A.V2 in PCOS cells and the decreased expression of miR-130b-3p in PCOS cells compared to normal are consistent with the disclosure in Figures 2A-2B of the instant application. Hence, the declarant’s statements regarding Modi’s teachings as being “unreliable and actually contradictory to the data” of the instant application are found factually incorrect.
Applicant also argues that “there would be no reasonable expectation of success”. In response, applicant’s attention is directed to the fact that the instant rejection is an anticipation rejection, not an obviousness rejection under §103. As such, a reasonable expectation of success is irrelevant irrespective of applicant’s personal opinion as the issue of a reasonable expectation of success is not a legal standard for anticipation under §102.
In view of the foregoing, this rejection is maintained.
Double Patenting
Claims 12-13, 17-18, and 22 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14-23 of U.S. Patent No. 9,676,844 B2 in view of Modi for the reasons as set forth in the Office action mailed on July 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on October 13, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims are distinguished from Modi. Contrary to applicant’s argument, the instant claims are not patentably distinct from the ‘844 patent claims in view of the teachings of Modi, wherein the teachings of Modi were grossly mischaracterized by the declaration in the §1.132 declaration as explained above, wherein Modi’s teachings are consistent with, not contrary to, the disclosure of the instant application regarding the overexpression of DENND1A.V2 and downregulation of miR-130b-3p in PCOS cells. Hence, this rejection is maintained.
Claims 12-13, 17-18, and 22 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 9,957,567 B2 in view of Modi for the reasons as set forth in the Office action mailed on July 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on October 13, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims are distinguished from Modi. Contrary to applicant’s argument, the instant claims are not patentably distinct from the ‘567 patent claims in view of the teachings of Modi, wherein the teachings of Modi were grossly mischaracterized by the declaration in the §1.132 declaration as explained above, wherein Modi’s teachings are consistent with, not contrary to, the disclosure of the instant application regarding the overexpression of DENND1A.V2 and downregulation of miR-130b-3p in PCOS cells. Hence, this rejection is maintained.
Claims 12-13, 17-18, and 22 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,723,790 B2 in view of Modi for the reasons as set forth in the Office action mailed on July 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on October 13, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims are distinguished from Modi. Contrary to applicant’s argument, the instant claims are not patentably distinct from the ‘790 patent claims in view of the teachings of Modi, wherein the teachings of Modi were grossly mischaracterized by the declaration in the §1.132 declaration as explained above, wherein Modi’s teachings are consistent with, not contrary to, the disclosure of the instant application regarding the overexpression of DENND1A.V2 and downregulation of miR-130b-3p in PCOS cells. Hence, this rejection is maintained.
Claims 12-13, 17-18, and 22 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 10,865,448 B2 in view of Modi for the reasons as set forth in the Office action mailed on July 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on October 13, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims are distinguished from Modi. Contrary to applicant’s argument, the instant claims are not patentably distinct from the ‘448 patent claims in view of the teachings of Modi, wherein the teachings of Modi were grossly mischaracterized by the declaration in the §1.132 declaration as explained above, wherein Modi’s teachings are consistent with, not contrary to, the disclosure of the instant application regarding the overexpression of DENND1A.V2 and downregulation of miR-130b-3p in PCOS cells. Hence, this rejection is maintained.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 12, 16, 18, and 21 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.
Claims 12 and 18 each recite “other PCOS gene products.” It is unclear what is encompassed by “other” as such gene products are not particularly and distinctly pointed out in the claims. As such, the metes and bounds pertaining to the aforementioned limitation cannot be clearly ascertained.
In the remarks filed on October 13, 2025, applicant argues that the aforementioned limitation is “clear and definite” by pointing out paragraph 00041 of the specification. In response, the paragraph pointed out by applicant does not whatsoever clearly define the aforementioned limitation as the paragraph expressly states that “other PCOS gene products such as LHCGR, DENND1A, and RAB5B, among others as described herein”. That is, the disclosure in the specification itself is ambiguous and unclear as evidenced by the phrase “such as” and “among others” and further in view of the disclosure of “DENND1A” (the generic term of the specifically claimed DENND1A.V2). It is highly questionable as to why the recited “other” genes in paragraph 00041 are not particularly and distinctly claimed in the instant claims if such term were so clear and definitive as argued by applicant. Again, the aforementioned limitation is not clearly defined in the specification, and the claims do not provide any clear definition of the “other PCOS gene products” to ascertain the clear scope/definition of such gene products.
Claim 16 recites the limitation "The method of claim 15" in line 1. There is insufficient antecedent basis for this limitation in the claim since claim 15 has been cancelled thus no longer exists.
Claim 21 recites the limitation "The method of claim 20" in line 1. There is insufficient antecedent basis for this limitation in the claim since claim 20 has been cancelled thus no longer exists.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 12-13, 17-18, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over McAllister et al. (Endocrinology, 2019, 160:1964-1981, of record) in view of Ghazzi et al. (US 2004/0029891 A1, of record).
See the priority benefit denial noted above.
McAllister teaches a method of diagnosing PCOS that is associated with DENND1A.V2 overexpression, wherein the PCOS diagnosis is made by detecting differentially downregulated expression level of miR-130b-3p in cells obtained from PCOS patients compared to normal cells, wherein the expression level of DENND1A.V2 negatively correlates with that of miR-130b-3p in PCOS such that the ratio of the expression level of DENND1A.V2 to that of miR-130b-3p in PCOS is higher compared to normal, healthy controls. See pages 1970-1971, 1975-1977; Table 1; Figures 2 and 4.
McAllister does not teach administering a therapeutic agent that increases fertility in a subject having been diagnosed with PCOS based on DENND1A.V2 overexpression and miR-130b-3p downregulation in cells obtained from the subject.
Ghazzi teaches that PCOS patients suffer from infertility due to PCOS and the patients having been diagnosed to have PCOS can be provided with the “treatment with a pyrazolopyrimidinone PDE V inhibitor”, which “leads to increased levels of uterine blood flow”, which “is associated with improved fertility in subjects with PCOS.” See paragraphs 0003-0015 and 0278-0281.
It would have been obvious to one of ordinary skill in the art before the effective filing date to follow McAllister’s PCOS diagnosis method with Ghazzi’s PCOS treatment method comprising administering an agent that improves fertility in the patient diagnosed to have PCOS. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because it is a normal desire of any relevant artisan in the pertinent art to provide appropriate treatments to a diagnosed patient and it would have been generally understood in the relevant art that the purpose of PCOS diagnosis is to identify a patient having PCOS for providing appropriate treatment for PCOS as evidenced by the teachings of Ghazzi.
Accordingly, claims 12-13, 17-18, and 22 taken as a whole would have been prima facie obvious before the effective filing date.
Response to Arguments
Applicant's arguments filed on October 13, 2025 have been fully considered but they are not persuasive. Applicant argues that the McAllister reference does not qualify as prior art in view of the declaration under 37 CFR 1.130(a). In response, it is noted that the declaration under 37 CFR 1.130(a) filed on October 13, 2025 is insufficient to disqualify the McAllister reference for the following reasons:
The declarant, one of the two co-inventors in the instant application and one of co-authors of the McAllister reference, states that only the two named co-inventors of the instant application “are the inventors of the inventive subject matter” and “the other authors of the article are identified as co-authors because of their contributions to the article”. In response, it is found that the McAllister reference expressly identifies the first three co-authors, Jan M. McAllister, Angela X. Han, and Bhavi P. Modi, as equal contributors of the research article by stating “J.M.A., A.X.H., and B.P.M. contributed equally as first authors.” See the footnote at page 1964. As such, it is ambiguous and highly doubtful as to the declarant’s statement that A.X.H. and B.P.M., who are not named co-inventors in the instant application, did not contribute any inventive effort pertaining to the subject matter relevant to the claimed PCOS diagnosis based on miR-130b-3p and DENND1A.V2 expression levels. That is, the credibility to the declarant’s statement excluding A.X.H. and B.P.M from the persons who contributed to the subject matter disclosed in the McAllister reference and relied on in this rejection is not compelling in view of the aforementioned footnote at page 1964. Taken together, the McAllister reference is deemed to qualify as a work of others thus is cited as a prior art in the instant rejection.
Conclusion
No claim is 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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/DANA H SHIN/Primary Examiner, Art Unit 1635