DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group III in the reply filed on 9/9/2026 is acknowledged. The traversal is on the ground(s) that Xie is silent regarding wherein the huMSCs overexpress miR144, BMP-2, TGFbeta1, IL-10, or any combination thereof, administer a different dosage, and are silent regarding co-culturing humans ovarian granulosa cells with the MSC, and are silent to use in preventing chemotherapy induced damage in a male This is not found persuasive because the special technical feature of the claims that is present in all of the claims. The only feature present in all the claims was MSC for therapeutic application. Not all claims required huMSCs overexpress miR144, BMP-2, TGFbeta1, IL-10, or any combination thereof, administer a different dosage, and are silent regarding co-culturing humans ovarian granulosa cells with the MSC, and are silent to use in preventing chemotherapy induced damage in a male. As such these limitation are not part of the unifying technical feature of the claims. Since Xie discloses a therapeutic application of huMSC, the technical feature common to all of the claims does not provide a novel contribution over the prior art.
The requirement is still deemed proper and is therefore made FINAL.
However, while search burden is not a consideration in lack of unity practices, Examiner has decided to rejoin groups I and III because in searching the exosomes, relevant prior art to both groups have been found.
Claims 23, 23, and 25-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 9/9/2026.
For the species election, Applicant elected the species of treating POI or PCOS with traverse. However, Applicant does not provide an rationale for traversing the species election. As such, species election will be treated as an election without traverse.
Claim 24 has been included in consideration of groups I and III because as Applicant elucidates in their remarks, this claims should be grouped with groups I and III, not group IV.
Claims 1, 2, 4, 9-15, 17-18, 20, and 24 are under consideration in this office action.
Claim Objections
Claims 1, and 10-13 are objected to because of the following informalities: Claim 1 recites limitation that have been withdrawn by restriction. Removing the limitations pertaining to non-elected subject matter would be remedial. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
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 1, 2, 4, 9-15, 17-18, 20, and 24 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.
Claim 1 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of “treating or preventing” is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: (1) “treating” and “preventing” method are structurally two different types of methods. “Treating” administers to patients have POI or PCOS. “Preventing” administers to a patient that does not POI or PCOS. As such, the two method types do not have a common structural element of functional element in common and thus is improper Markush groupings. (2) POI or PCOS distinctly different conditions that have different pathologies and etiologies. As such, the have not single structural similarity and common use that flows from that structure. As such, POI or PCOS is also an improper Markush grouping.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
The remaining claims depend upon claim 1 and thus also comprise these improper Markush groupings.
Regarding claim 14, it recites, “administering is from about 6E10 to about 6E12”. This appears to be some type of abbreviation regarding exosome. In the specification it appears to possibly be some measure of amount or concentration. It is not a standard nomenclature known in the art and the specification does not define “6E10” and “6E12”. As such, the meaning and metes and bound of the recitation cannot be determined. For purposes of applying art to this claim, if exosome are administered to a POI or PCOS mammal, limitations of claim 14 will be deem to have been meet by the art.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/218793, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. This provisional application solely describes MSC that overexpress miR144 and not of the other recited factors (b)-(e) of the claims. As such, only the embodiment for MSC that overexpress miR144 are granted prior to the earlier filing date:7/6/2021. All other embodiments (b)-(e) are denied the benefit of this application’s earlier filing date and have an effective filing date of 8/24/2021.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
(1) Claim(s) 1, 2, 4, 9-10, 14-15, and 17-18, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang (Yang et al. Laboratory Investigation 2020. 100:342-352, first published online 9/19/2019; of record in IDS 2/13/2024).
Regarding claim 1, Yang discloses a POF rat model produced by intraperitoneal injection of CTX (p. 343, col 2). These disclosures expressly disclose premature ovarian insufficiency (POI) in a female mammal as claimed. Yang discloses collecting exosomes from BMSC and transplanting both BMSC and exosome derived from BMSC into the POF rat model (p. 344, col 1). These disclosures disclose administering to the female mammal an effective amount of MSC and exosome product by MSC. Yang discloses in their study, they show that BMSC and BMSC-derived exosome transplantation can significantly recover the estrus cycle, increase the number of basal and sinus follicles in POF rats, increase estradiol (E₂) and anti-Mullerian hormone (AMH) levels, and reduce follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in the serum. Furthermore, we demonstrate that BMSC-derived exosomes prevent ovarian follicular atresia in cyclophosphamide (CTX)-treated rats via the delivery of miR-144-5p, which can be transferred to cocultured CTX-damaged granulosa cells (GCs) to decrease GC apoptosis. A functional assay revealed that overexpression of miR-144-5p in BMSCs showed efficacy against CTX-induced POF, and the improvement in the repair was related to the inhibition of GC apoptosis by targeting PTEN. The opposite effect was exhibited when miR-144-5p was inhibited. Taken together, our experimental results provide new information regarding the potential of using exosomal miR-144-5p to treat ovarian failure (abstract). These disclosure expressly disclose exosome produced by MSC that overexpress miR144 as claimed and treatment of multiple symptoms of POI. Thus, Yang expressly discloses claims 1.
Regarding claim 2, Yang discloses administering MSC as discussed above.
Regarding claim 4, Yang discloses administering exosomes as discussed above.
Regarding claims 9 and 10, Yang discloses administering exosome comprising the effector miR144 as discussed above.
Regarding claim 14, Yang discloses administering exosome meeting the limitation of the claims, given the indefinite nature of this claim (see claim interpretation in indefiniteness rejection above).
Regarding claim 15, Yang discloses MSC derived from bone marrow as discussed above.
Regarding claim 17, Yang discloses treating POI as discussed above.
Regarding claim 18, Yang discloses that the POI induced by CTX, a chemotherapeutic agent, as discussed above.
(2) Claim(s) 1, 2, 4, 12, 14-15, , is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xie (Xie et al. Hindawi Stem Cells International 2019, pp.1-12, of record in IDS 2/13/2024), as evidenced by Salazar (Salazar et al. Am J Physiol Lung CellMol Physiol 297: L1002–L1011, 2009).
Regarding claim 1, Xie discloses administering MSC to a DHEA induce PCOS mouse (page 2, section 2). Xie teaches that the administered MSCs resulted in a reducing on local and systemic inflammatory responses present in PCOS (abstract). As such, Xie expressly discloses a method of treating PCOS comprising administering MSC. Xie is silent as to MSC overexpressing miRNA BMP-2, TGFbeta1, and/or IL10. However, Salazar states MSC derived from human umbilical cord blood (CB) or from the bone marrow of mice release Wnts 1, 2, and 7b, TGF-beta1, and PDGF-AA (p. L1002). Neither the claim nor the specification define the term, “overexpressing”. Further, the claim does not recite any structural elements introduced into the MSC that would impart exogenous overexpression of TGF-beta-1. As such, overexpressing can be interpreted as any amount of expression relative to no expression. Since, MSC express and release TGF-beta1, inherently the MSC described by Xie are MSC overexpressing TGF-beta 1 as claimed. Further, it is noted that the claims do recited that the exosomes of produced by the MSC are isolated. As such, the disclosure of MSCs also comprises all contents of MSC including exosome produced by MSCs. As such, Xie also discloses administering the MSC exosome. As such, Xie expressly or inherently discloses all of the limitations of claim 1.
Regarding claim 2, Xie discloses administering MSC as discussed above.
Regarding claim 4, Xie discloses administering exosomes as discussed above.
Regarding claim 12, Xie discloses administering MSC overexpressing TGFbeta1 inherently as describe above as well as exosomes from said MSC.
Regarding claim 14, Xie discloses administering exosomes as discussed above.
Regarding claim 15, Xie discloses BMSC (page L1002).
Regarding claim 20, Xie discloses PCOS as discussed above.
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.
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang (Yang et al. Laboratory Investigation 2020. 100:342-352, first published online 9/19/2019; of record in IDS 2/13/2024).
The claims of claim 24 is taught by Yang as discussed above. Yang does not teach that the POF subject is a human. However, Yang does teach that chemotherapy induced premature ovarian failure (POF) is women is currently clinically irreversible. Bone marrow MSC are a promising cellular strategy for POF (abstract). Yang further teaches our studies indicate the therapeutic potential of BMSC derived exosomal miR-144- in POF treatment. P. 343, col 1, last part).
Thus it would have been obvious to an artisan of ordinary skill before the effective filing date to apply the BMSC and/or exosome therapy, successful in animals models, taught by Yang to humans with a reasonable expectation of success. An artisan would be motivated to do so because Yang teaches a clear desire to extend this methodology to humans and described the methodology as promising for treatment in human. As such, Yang renders claim 24 obvious.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
