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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/10/2026 has been entered.
Status of the Claims
Claims 1-4, 7, 9-11, 13, 17, 19, 29, 32, 35, and 39 are currently pending.
Claim 1 is amended.
Claims 19, 29, 32, 35, and 39 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 5-6, 8, 12, 14-16, 18, 20-28, 30-31, 33-34, 36-38, and 40-46 are cancelled.
Claims 1-4, 7, 9-11, 13, and 17 have been considered on the merits.
Withdrawn Rejections
The rejection made under 35 U.S.C. 112(a) is withdrawn in light of the amendments and Remarks submitted on 02/10/2026.
New and Maintained Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 102
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 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.
Claims 1-3, 10, 13, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xiong et al (Xiong, Zhi-Hui, et al. Biomedicine & Pharmacotherapy 105 (2018): 1240-1247.), reference of record.
Regarding claim 1, Xiong teaches a method of treating placental preeclampsia by administering an effective amount of mesenchymal stem cell (MSC) derived exosomes to a female subject (pg. 1242, col. 1, para 1-3). Xiong teaches that “the decidua of rats in PE group and PE+NC group was swollen and thickened with obvious inflammatory cell infiltration, basal zone trophoblast giant cell hyperplasia, increased vacuolated cell and thickened basal zone. The labyrinth zone trophoblast also showed cell hyperplasia, some edema and thickened plasma membrane. The pathological changes in L-Exo group, M-Exo group and H-Exo group were alleviated than those in the PE group and PE+NC group (Fig. 5D)” (Pg. 1244, col. 1, last para; and Fig. 5D). Xiong’s statement meets the limitation of “wherein the MSC exosome reduces intrauterine inflammation” because Xiong describes the preeclampsia (PE) and negative control groups as having “obvious inflammatory cell infiltration” in the decidua, which meets the limitations of inflammation, and that in the treatment groups L-Exo, M-Exo, and H-Exo the pathological changes were alleviated, which meets the limitation of the MSC exosome reducing intrauterine inflammation.
Regarding claim 2, The MSC exosomes are isolated from MSC-conditioned media (pg. 1241, col. 2, para 2).
Regarding claim 3, The MSCs are isolated from umbilical cord (i.e. Wharton’s jelly of the umbilical cord) (pg. 1241, col. 1, para 3).
Regarding claim 10, Xiong teaches that the exosomes are administered repeatedly (pg. 1242, col. 1, para 3).
Regarding claim 13, Xiong teaches that the exosomes are administered antepartum (i.e before birth) (pg. 1242, col. 1, para 3).
Regarding claim 17, Xiong teaches evidence that the exosomes reverse preeclampsia related symptoms and reduce the likelihood of fetal growth restriction and/or fetal loss which can be see through the placentas which are treated with the high concentration of exosomes that revert back to a normal level (see fig. 5 comparison between PE, normal, and high-exosome treatment).
Therefore, Xiong anticipates the claims.
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 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Xiong et al (Biomedicine and Pharmacotherapy, 2018), reference of record.
Regarding claim 4, the limitations of the independent claim are taught by Xiong above. Xiong does not teach that the female subject is a human subject as required by claim 4.
However, Xiong teaches that their “results suggest that hucMSC-Ex may be an alternative approach for the therapy of PE” (pg. 1246, col. 1, last para). Additionally, Xiong states that clinical treatment requires more investigation and confirmation (pg. 1246, Col. 2, first para). Therefore, Xiong is suggesting the application of their method in human clinical treatment.
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of treatment taught by Xiong with the suggestion that this method may be an alternative treatment approach to PE and that clinical treatment should be investigated taught by Xiong to arrive at the instant invention.
One of ordinary skill in the art would be motivated to make this combination because Xiong teaches that their “results suggest that hucMSC-Ex may be an alternative approach for the therapy of PE” (pg. 1246, col. 1, last para). Additionally, Xiong states that clinical treatment requires more investigation and confirmation (pg. 1246, Col. 2, first para). Therefore, Xiong is suggesting the application of their method in human clinical treatment.
One of ordinary skill in the art would have a reasonable expectation of success when combining Xiong with Xiong because Xiong teaches the necessary steps of the method applied to a rat model of preeclampsia and Xiong teaches that evidence demonstrates that exosomes from MSCs can exert positive roles in tissue injury repair and exosomes have been reported to be implicated in the treatment of various diseases (pg. 1241, Col. 1, para 1).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1, 7, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Xiong et al (Biomedicine and Pharmacotherapy, 2018), as applied to claim 1-3, 5-6, 8, 10, 13, and 15-17 above, and further in view of Huang et al (Stem cell Research, 2018).
Regarding claims 7 and 9, the limitations of the independent claim are taught by Xiong above. Xiong does not teach that the subject suffers from infertility as required by claim 7. Xiong does not teach that the subject is administered the exosome composition only once as required by claim 9.
However, Huang teaches about exosomes derived from human adipose tissue and their ability to treat ovarian insufficiency (i.e. infertility) in mice. Huang teaches that the mice subjects have premature ovarian insufficiency (POI) as required by claim 7 (abstract). Further, Huang teaches that the mice are treated through the delivery of MSC exosomes in a single administration as required by claim 9 (pg. 3, col. 2, para 3). Huang teaches that exosomes derived from hADSCs improved ovarian function of POI disease via regulation of the SMAD signaling pathway (abstract).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of treatment taught by Xiong with the subject and administration frequency taught by Huang to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Huang teaches that exosomes derived from hADSCs improved ovarian function of POI disease via regulation of the SMAD signaling pathway (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Xiong with Huang because both teach method of treating female reproductive organs with MSC derived exosomes.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Xiong et al (Biomedicine and Pharmacotherapy, 2018), as applied to claim 1-3, 5-6, 8, 10, 13, and 15-17 above, and further in view of Azizi et al (Biomedicine and Pharmacology, 2018).
Regarding claim 11, the limitations of the independent claim are taught by Xiong above. Xiong does not teach that the exosomes are administered via intravenous or intrauterine injection as required by claim 11.
However, Azizi teaches about stem cell based therapies in the female reproductive organs (abstract/ Fig. 1). Azizi teaches that the “injection of stem cells can be through both the veins and into the uterus but has been demonstrated that intrauterine injections are more effective and also is a standard method” as required by claim 11 (Fig. 1 description).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of treatment taught by Xiong with the administration method taught by Azizi to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Azizi teaches that the “injection of stem cells can be through both the veins and into the uterus but has been demonstrated that intrauterine injections are more effective and also is a standard method”(Fig. 1 description). One of ordinary skill in the art would have a reasonable expectation of success when combining Xiong with Azizi because Xiong teaches the necessary steps of the method and Azizi teaches that intrauterine injection of stem cells is the standard method (Fig. 1 description).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments, see Remark, pgs. 5-6, filed 02/10/2026, with respect to the 35 U.S.C. 112(a) enablement rejection have been fully considered and are persuasive. The rejection has been withdrawn.
Applicant's arguments filed 02/10/2026, regarding the 35 U.S.C. 102 and 103 rejections, have been fully considered but they are not persuasive.
Applicant argues (Remarks, pg. 7), regarding the 35 U.S.C. 102 rejection, that Xiong does not teach the claim limitation of the exosomes reducing intrauterine inflammation. Applicant argues that Xiong discloses that the labyrinth zone trophoblasts showed “cell hyperplasia, some edema and thickened plasma membrane” and concludes that Xiong therefore teaches reduced interstitial edema but not reduction of intrauterine inflammation.
In response, the argument is not found persuasive. Xiong states that “the decidua of rats in PE group and PE+NC group was swollen and thickened with obvious inflammatory cell infiltration, basal zone trophoblast giant cell hyperplasia, increased vacuolated cell and thickened basal zone. The labyrinth zone trophoblast also showed cell hyperplasia, some edema and thickened plasma membrane. The pathological changes in L-Exo group, M-Exo group and H-Exo group were alleviated than those in the PE group and PE+NC group (Fig. 5D)” (Pg. 1244, col. 1, last para; and Fig. 5D). Xiong’s statement meets the limitation of “wherein the MSC exosome reduces intrauterine inflammation” because Xiong describes the preeclampsia (PE) and negative control groups as having “obvious inflammatory cell infiltration” in the decidua, which meets the limitations of inflammation, and that in the treatment groups L-Exo, M-Exo, and H-Exo the pathological changes were alleviated, which meets the limitation of the MSC exosome reducing intrauterine inflammation. Therefore, the argument is not found persuasive.
Applicant argues (Remarks, pg. 8), in reference to the 35 U.S.C. 103 rejections, that for at least the reasons discussed in the arguments regarding the 35 U.S.C. 102 rejection employing Xiong that the 35 U.S.C. 103 rejections should be withdrawn.
In response, this argument is not found persuasive. The arguments regarding Xiong have been addressed at point 20 above and were found unpersuasive. Therefore, this argument is not found persuasive.
Conclusion
No claims are allowed.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632