DETAILED ACTION
Claim Status
As of the Non-Final Office Action mailed 9/25/2025, claims 1-20 were pending.
In Applicant's Response filed on 2/24/2026, claims 1-20 were canceled and claims 21-34 were newly added.
As such, claims 21-34 are pending and have been examined herein.
Withdrawn Objections/Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
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.
Claim 26 is 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 26 recites, inter alia, “wherein the ovarian microenvironment is characterized by upregulated production of interleukin-27 as compared to a microenvironment of a non- degenerative ovary”. It is unclear how an ovarian microenvironment of ovarian failure has upregulated interleukin-27 production when ovarian failure (commonly known as premature ovarian insufficiency) is characterized by impaired or deficient IL-27 signaling. Thus, the claim is indefinite. Given this discrepancy, claim 26 has not been rejected in the art rejections below absent a showing of evidence to the contrary.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to rejections made based on said interpretations. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
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.
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.
Claim(s) 21-25, and 27-34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ichim et al (US10792310B2, 7/17/2017; published 10/6/2020) ) as evidenced by Hoek et al (Endocr Rev. 1997 Feb;18(1):107-34), Nouri et al (J Reprod Immunol. 2024 Sep; 165:104290), in view of Bahir et al (In Regenerative Medicine. IntechOpen. 17 July 2020).
Ichim teaches method for treatment of premature ovarian failure (abstract). The reference teaches method for addressing ovarian aging or premature ovarian failure in an individual through the steps of: a) diagnosing an individual with premature ovarian failure or ovarian aging; b) administering endothelial progenitor cells to said individual; c) administering mesenchymal stem cells to said individual; and, d) measuring ovarian function following administration of said cell populations to said individual (see claim 2 of Ichim). MSC are injected into the ovaries through laparoscopy. MSC population can be derived from sources selected from the group consisting of: bone marrow, adipose tissue, umbilical cord blood, placental tissue, etc. Steroidal-cell antibodies were detected in ovarian biopsies performed in s a small cohort of women with spontaneous POI, 100% of women with SCAs were found to have CD3+ lymphocytic infiltrates on ovarian biopsy, indicative of T-cell-mediated oophoritis (“enhanced T cell infiltration as compared to a microenvironment of a non-degenerative ovary” as in instant claim 22; “wherein the ovarian microenvironment is associated with enhanced gamma delta cell infiltration as compared to a microenvironment of a non-degenerative ovary” as in instant claim 24). The disclosure reads on “A method of treating ovarian failure in a mammal in need comprising: a) selecting a mammal suffering from ovarian failure within an ovarian microenvironment; b) providing a population of mesenchymal stem cells (MSCs) derived from one or more of: i) natural MSCs derived from umbilical cord; ii) natural MSCs derived from placental tissue; . . . and d) administering a therapeutically effective amount of said . . . MSCs to said mammal via intra-ovarian injection.” as in instant claim 21 in-part.
Regarding claim 27, Ichim teaches that the mesenchymal stem cell population preferably expresses one or more markers selected from the group consisting of: STRO-1, CD105, CD54, CD106, HLA-I markers, vimentin, ASMA, collagen-1, fibronectin, LFA-3, ICAM-1, PECAM-1, P-selectin, L-selectin, CD49b/CD29, CD49c/CD29, CD49d/CD29, CD61, CD18, CD29, thrombomodulin, telomerase, CD10, CD13, STRO-2, VCAM-1, CD146, and THY-1 (i.e., CD90), which reads on “wherein said hypoxic-cultured MSCs possess one or more markers selected from the group consisting of: . . . g) CD90; h) CD105” as instantly claimed.
Evidentiary reference Hoek teaches premature ovarian failure and ovarian autoimmunity. Immunohistochemical analysis of the lymphocytic oophoritis (a cause of ovarian failure) reveals that the inflammatory cells are mainly formed by T lymphocytes (CD41 and CD81) with a few B cells, together with large numbers of plasma cells. Macrophages and NK cells can also be found (“wherein the ovarian microenvironment is characterized by enhanced NK cell infiltration as compared to a microenvironment of a non-degenerative ovary” as in instant claim 23).
Evidentiary reference Nouri states that folliculogenesis is the process where follicles in the ovaries develop and eventually lead to ovulation. Any disruption to this process can cause premature ovarian failure. miR-326 is one of the microRNAs whose expression leads to Th17 production. Th17 activates the immune system to respond more vigorously, and by producing interleukins and cytokines causes inflammation and autoimmune disorders. Th17-induced inflammation and Th17/Treg imbalance can result in POF. This investigation took samples from 30 POF patients and 30 healthy people. The study utilized PCR to assess the expression levels of cytokines, specific transcription factor (ROR-γt), and miR-326. Additionally, ELISA was employed to analyze serum levels of IL-17, IL-21, IL-23. Furthermore, flow cytometry was utilized to determine the frequency of Th17. Compared to the control group, our results demonstrated a rise in the transcription factor RORɣt and a considerable rise in the frequency of Th17 cells in patients with POF. The level of inflammatory cytokines IL-17, IL-21, and IL-23 secreted in serum samples of patients with POF increased significantly compared to the control group. This shows that those with POF have elevated IL-17 (“wherein the ovarian microenvironment is characterized by upregulated production of interleukin-17 as compared to a microenvironment of a non- degenerative ovary” as in instant claim 25).
The difference between Ichim and the instantly claimed invention is that it does not teach culturing the mesenchymal stem cells under hypoxic conditions between 1-10% oxygen (as in instant claim 21 in-part).
Bahir teaches that hypoxic preconditioning of MSCs improves their regenerative potential. Hypoxic preconditioning improves survival and stemness of cells and has been investigated in a number studies. SOX2, OCT4, NANOG and c-Myc are the markers that show stemness of cells (Section 5.1, para 1). It has been found that stem cells grown in hypoxia are more viable, have decreased apoptosis through effects on HIF1a and p53 pathways (same para). Hypoxia (1%) results in decreased senescence, increased lifespan of mesenchymal stem cells and were able to maintain proliferation rate, morphology and genetic stability (para 3). Stemness of MSCs remains preserved in hypoxic cultures. Hypoxia results in decreased expression of apoptotic BCL-2 and CASP3 and increased expression of anti-apoptotic genes (same para). This reads on “culturing the mesenchymal stem cells under hypoxic conditions between 1-10% oxygen” as in instant claim 21 in-part; “wherein the hypoxic-culturing induces enhanced Hypoxia- Inducible Factor-la (HIF-la) production from the MSCs compared to normoxia” as in claim 30; “wherein the hypoxic-culturing is about 2% oxygen” as in claim 31; “wherein the MSCs undergo hypoxic-culturing for at least 24 hours” as in claim 32; and “wherein the administered MSCs are resistant to apoptosis in the ovarian microenvironment” as in claim 34.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to administer MSCs to treat ovarian failure as taught by Ichim, where the MSC are preconditioned with hypoxia as taught by Bahir, to arrive at the instantly claimed invention. Bahir shows MSCs can be preconditioned with varying ranges of hypoxic conditions. One of ordinary skill would have been motivated to modify the MSCs of Ichim to include hypoxic preconditioning as taught by Bahir with a reasonable expectation of advantageously decreasing senescence, increasing lifespan of mesenchymal stem cells with maintained proliferation rate, morphology and genetic stability as taught by the prior art.
Regarding claim 28-29, neither Ichim nor Bahir explicitly teach “wherein said hypoxic-cultured MSCs inhibits cytokine production from helper T1 cells within the ovarian microenvironment” as in instant claim 28 and “wherein said inhibited cytokine is interferon gamma” as in instant claim 29. However, the claims are an intended result of the instantly claimed active method step. Thus, absent evidence to the contrary, the administered cells of Ichim and Bahir in combination would result in inhibition of cytokine production (including, but not limited to, interferon gamma).
Regarding claim 33, neither Ichim nor Bahir explicitly teach “wherein the administered MSCs induce T regulatory cell production in the ovarian microenvironment” as in instant claim 33. However, the claim is an intended result of the instantly claimed active method step. Thus, absent evidence to the contrary, the administered cells of Ichim and Bahir in combination would result in induction of T reg cell production.
Response to Arguments
The rejection(s) of previously pending claim(s) 1-20 are under 112(a) written description and enablement are moot in view of their cancellation. However, Applicant’s arguments, see Remarks and Declaration submitted by Dr. Amit Patel, filed 2/24/2026 are reasonably pertinent to newly pending claims 21-34. These arguments have been fully considered and are persuasive related to enablement and written description.
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.
Claim 21, 30-32, and 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of U.S. Patent No. 10,792,310 B2 in view of Bahir et al (In Regenerative Medicine. IntechOpen. 17 July 2020).
Claim 2 of U.S. Patent ‘310 is drawn to “A method for addressing ovarian aging or premature ovarian failure in an individual through the steps of: a) diagnosing an individual with premature ovarian failure or ovarian aging; b) administering endothelial progenitor cells to said individual; c) administering mesenchymal stem cells to said individual; and, d) measuring ovarian function following administration of said cell populations to said individual.” This reads on “A method of treating ovarian failure in a mammal in need comprising: a) selecting a mammal suffering from ovarian failure within an ovarian microenvironment; b) providing a population of mesenchymal stem cells (MSCs) derived from one or more of: i) natural MSCs derived from umbilical cord; ii) natural MSCs derived from placental tissue; . . . and d) administering a therapeutically effective amount of said . . . MSCs to said mammal via intra-ovarian injection” as in instant claim 21 in-part.
Bahir teaches that hypoxic preconditioning of MSCs improves their regenerative potential. Hypoxic preconditioning improves survival and stemness of cells and has been investigated in a number studies. SOX2, OCT4, NANOG and c-Myc are the markers that show stemness of cells (Section 5.1, para 1). It has been found that stem cells grown in hypoxia are more viable, have decreased apoptosis through effects on HIF1a and p53 pathways (same para). Hypoxia (1%) results in decreased senescence, increased lifespan of mesenchymal stem cells and were able to maintain proliferation rate, morphology and genetic stability (para 3). Stemness of MSCs remains preserved in hypoxic cultures. Hypoxia results in decreased expression of apoptotic BCL-2 and CASP3 and increased expression of anti-apoptotic genes (same para). This reads on “culturing the mesenchymal stem cells under hypoxic conditions between 1-10% oxygen” as in instant claim 21 in-part; “wherein the hypoxic-culturing induces enhanced Hypoxia- Inducible Factor-la (HIF-la) production from the MSCs compared to normoxia” as in claim 30; “wherein the hypoxic-culturing is about 2% oxygen” as in claim 31; “wherein the MSCs undergo hypoxic-culturing for at least 24 hours” as in claim 32; and “wherein the administered MSCs are resistant to apoptosis in the ovarian microenvironment” as in claim 34.
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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/G.R./Examiner, Art Unit 1632
/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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