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 was filed Oct. 6, 2021, and is a 371 application of PCT/KR2020/006574 filed on May 20, 2020, which claims benefit to the foreign application KR10-2019—0068042 filed on June 10, 2019.
Claim Status
In the response filed on Jan. 6, 2026, Applicant has amended claim 10 and cancelled claims 1-9 and 13.
Claims 10-12 and 14-17 are under examination in this Office Action.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The rejection of claims 10 and 14-17 under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as based on a disclosure which is not enabling is withdrawn due to Applicants amendments to the claims. The independent claims has been amended to a method for promoting production of stem cell-derived exosomes and therefore do not require the step of obtaining stem cell-derived exosomes.
The rejection of claims 10-11, and 14-17 are rejected 35 U.S.C. 102(a)(1) as being anticipated by Stice, et al. (US2018/0327714A1, published 2018, prior art of record), is withdrawn due to Applicants amendments to the claims. The independent claims has been amended to pretreating stem cells and requiring a pretreatment agent of at least hyaluronic acid or lanifibranor.
The rejection of claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Stice, et al. (US2018/0327714A1, published 2018, prior art of record), as applies to claims 10-11, and 14-17, in further view of Wiklander, et al. (Journal of extracellular vesicles 4.1: 26316; published 2015, prior art of record), is withdrawn due to Applicants amendments to the claims. The independent claims has been amended to pretreating stem cells and requiring a pretreatment agent of at least hyaluronic acid or lanifibranor.
The rejection of claims 10-12, and 14-17 are rejected 35 U.S.C. 103 as being unpatentable over Yi, Yong Weon and Cho, Byong Seung (WO2019/031729A1, published Feb. 14, 2019, hereinafter as “Yi”), Wettstein, Guillaume, et al. (Hepatology communications 1.6: 524-537, published 2017, hereinafter as “Wettstein”), Wiklander, et al. (Journal of extracellular vesicles 4.1: 26316; published 2015, prior art of record), is withdrawn due to Applicants amendments to the claims. The independent claims has been amended to pretreating stem cells and requiring a pretreatment agent of at least hyaluronic acid or lanifibranor.
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.
Claims 10 and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gerecht, et al. (Proceedings of the National Academy of Sciences 104.27: 11298-11303, published 2007).
This is a new rejection as necessitated by amendment to the claims submitted on Jan 6, 2026.
Providing guidance on instances where the method steps of the prior art and instant claims are the same, Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) states “[T]hat since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims.” In the instant case, the claim recites “promoting production of stem cell-derived exosomes”. Thus, the claim does not require a step for stem cell-derived exosomes to actually be obtained in the method.
Regarding claim 10, Gerecht discloses a method for promoting production of stem cell-derived exosomes, the method comprising a step of: pretreating stem cells by culturing stem cells in a cell culture medium containing hyaluronic acid as a pretreatment agent (see e.g. abstract, pages 11301-11303, and figs. 4-5).
Regarding claim 14, Gerecht discloses wherein the stem cell is an embryonic stem cell (see e.g. abstract, pages 11301-11303, and figs. 4-5).
Thus, the instant claims are anticipated by Gerecht.
Claim 10, 14-15, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Corradetti, et al. (Scientific reports 7.1: 7991, published 2017).
This is a new rejection as necessitated by amendment to the claims submitted on Jan 6, 2026.
Providing guidance on instances where the method steps of the prior art and instant claims are the same, Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) states “[T]hat since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims.” In the instant case, the claim recites “promoting production of stem cell-derived exosomes”. Thus, the claim does not require a step for stem cell-derived exosomes to actually be obtained in the method.
Regarding claim 10, Corradetti discloses a method for promoting production of stem cell-derived exosomes, the method comprising a step of: pretreating stem cells by culturing stem cells in a cell culture medium containing hyaluronic acid as a pretreatment agent (see e.g. abstract, pages 3-4 and 7-10, figs. 1-6).
Regarding claims 14-15, Corradetti discloses wherein the stem cell is an adult stem cell and wherein the adult stem cell is a mesenchymal stromal cell of animal tissue origin (see e.g. abstract, pages 3-4 and 7-10, figs. 1-6).
Regarding claims 17, Corradetti discloses wherein the adult stem cell of animal tissue origin is of a hematopoietic stem cell (i.e. bone marrow).
Thus, the instant claims are anticipated by Corradetti.
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.
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.
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 10-12, and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Stice, et al. (US2018/0327714A1, published 2018, previously presented), in view of Corradetti, et al. (Scientific reports 7.1: 7991, published 2017), and Wiklander, et al. (Journal of extracellular vesicles 4.1: 26316; published 2015, previously presented).
This is a new rejection necessitated by amendment to the claims. However, since it contains prior art previously set forth in the non-final Official action mailed on Dec. 10, 2024, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
Regarding claim 10, Stice discloses a method for promoting production of stem cell-derived exosomes (see e.g. abstract), the method comprising a step of: culturing stem cells (e.g. mesenchymal stem cells) with hyaluronan (i.e. hyaluronic acid, HA)(see e.g. abstract, and para. 3-8, 62, 85, page 8, claim 11).
Stice is silent regarding hyaluronan (i.e. HA) as a pretreatment agent for pretreating the stem cells in a cell culture medium.
However, the prior art of Corradetti discloses pretreating stem cells with HA as a pretreatment agent in a cell culture medium (see e.g. page 4-7, fig. 6).
Accordingly, it would have been obvious to a person of ordinary skill in the art to modify the stem cell-derived exosome methods as taught by Stice with pretreating the stem cells with hyaluronic acid as taught by Corradetti because both Stice and Corradetti are methods directed to improving therapeutic delivery of cells for regenerative medicine (see e.g. para. 146 and abstract, respectively). Further, both Stice and Corradetti disclose methods using mesenchymal stem cells (i.e. MSC) and hyaluronic acid (i.e. HA)(see e.g. para. 85 of Stice and abstract of Corradetti). Corradetti discloses that hyaluronic acid improves MSC homing towards the site of inflammation (see e.g. abstract). Further, Corradetti discloses increased accumulation for HA-treated MSC yielded a substantial reduction in inflammation as demonstrated by the decrease in the expression of pro-inflammatory markers and by the induction of a pro-regenerative environment (see e.g. abstract). Thus, a person of ordinary skill in the art would have had predictable results with a reasonable expectation of success because Stice discloses mesenchymal stem cell-derived exosomes homing to damaged tissue and Corradetti discloses methods for homing mesenchymal stem cells to the site of inflammation (see e.g. para. 152 and page 1, respectively).
Regarding claim 11, Stice discloses that human pluripotent stem cells (hPSC) were washed with PBS, corresponding to the claim limitation of washing the cultured stem cells (See e.g. para 122, Example 1). Further, Stice discloses an additional culturing in a cell culture medium to obtain exosomes (i.e. EV) (See e.g. para. 122-123, Example 1).
Regarding claim 12, Stice teaches a preferred media that is a low protein, serum-free based growth medium that supports stem cells (i.e. mesenchymal stem cells)(e.g. fetal bovine serum)(see e.g. para. 59-60, Example 1).
Stice does not explicitly state that the serum-free media is free of exosomes.
However, Stice cites the prior art of Wiklander, which discloses a culture medium contains fetal bovine serum (FBS) depleted of serum EVs (see e.g. page 2, col. 2).
Accordingly, it would have been obvious to a person of ordinary skill in the art to culture the stem cells with a fetal bovine serum that was free of exosomes as taught by Wiklander in the method of Stice because Wiklander teaches the use of fetal bovine serum free of exosomes would allow for an optimal number of cells to be obtained (i.e. 90% confluency)(see e.g. page 2). An artisan of ordinary skill in the art of (i.e. cell culture conditions) would have done routine optimization for obtaining a pure population of exosomes and has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007)). In the instant case, it could have been done with predictable results with a reasonable expectation of success because the prior art of Stice references Wiklander (para. 68) for teaching the methods of culturing the stem cells. Thus, a person of ordinary skill in the art would have been able to optimize the cell culture medium conditions for obtaining stem cell-derived exosomes in a cell culture medium that contains fetal bovine serum (FBS) depleted of serum exosomes with a reasonable expectation of success.
Regarding claim 14, Stice discloses wherein the stem cell is an embryonic stem cells (ESC), adult stem cells, induced pluripotent stem cell (iPSC) or mesenchymal stem cells (see e.g. page 41).
Regarding claim 15, Stice discloses wherein the adult stem cell is an induced pluripotent stem cell of human tissue origin (see e.g. para. 49-52).
Regarding claim 16, Stice discloses wherein the human tissue is selected from the group consisting of umbilical mesenchymal stem cells (MSCs)(i.e. umbilical cord or umbilical cord blood) (see e.g. para. 23, Fig. 5).
Regarding claim 17, Stice discloses wherein the adult stem cell of human origin is selected from neural stem cells (see e.g. para. 41).
Thus, the instant claims are prima facie obvious absent evidence to the contrary.
Response to Traversal:
Applicant argues that Stice and Wiklander fails to disclose all elements of the instant claims (Remarks, page 6). Applicant argues that Stice does not describe hyaluronan as a pretreatment agent. Applicant argues that Wiklander fails to remedy the deficiencies of Stice, because Wiklander is silent regarding promoting production of stem cell-derived exosomes and pretreatment of stem cells using agents such as hyaluronic acid and lanifibranor (Remarks, page 7).
Applicants’ arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
Applicant’s arguments rely on language recited in preamble recitations in claim independent claim 10 (i.e. promoting production). When reading the preamble in the context of the entire claim, the recitation of promoting production of stem cell-derived exosomes is not limiting because the body of the claim describes a complete invention, and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02. In the instant case, the new anticipation rejections of Gerecht, et al. (Proceedings of the National Academy of Sciences 104.27: 11298-11303, published 2007) and Corradetti, et al. (Scientific reports 7.1: 7991, published 2017) are necessitated by amendment to the claims submitted on Jan 6, 2026. Providing guidance on instances where the method steps of the prior art and instant claims are the same, Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) states “[T]hat since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims.” In the instant case, the claim recites “promoting production of stem cell-derived exosomes”. Thus, the claim does not require a step for the “stem cell-derived exosomes” to actually be obtained in the claimed method.
In response to applicants’ argument regarding the prior art of Stice, as discussed above, Stice is cited for disclosing a method for production of stem cell-derived exosomes, and the prior art of Corradetti is cited for suggesting pretreating stem cells with HA as a pre-treatment agent in a cell culture medium (see e.g. page 4-7, fig. 6 of Corradetti). A person of ordinary skill in the art would have combined the method of Stice with the method of Corradetti because Stice discloses mesenchymal stem cell-derived exosomes homing to damaged tissue and Corradetti discloses methods for homing mesenchymal stem cells to the site of inflammation (see e.g. para. 152 and page 1, respectively). Thus, a person of ordinary skill in the art would have had predictable results with a reasonable expectation of success. In response to applicant's argument that Stice discloses exosomes that are in or on a biocompatible scaffold comprising hyaluronic acid, it is noted that the claims read on “comprising” which does not exclude other embodiments, such as the addition of a biocompatible scaffold (see MPEP 2111.03).
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 the instant case, Wiklander is cited for discloses a cell culture medium containing fetal bovine serum free of exosomes, and the prior art of Stice and Corradetti are cited for promoting production of stem cell-derived exosomes and pretreatment of stem cells using agents such as hyaluronic acid, as discussed above.
In response to Applicant arguments that there is no motivation to supplement the missing features above because both references are silent regarding hyaluronic acid and lanifibranor, 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 prior art of Stice discloses hyaluronic acid, as discussed above. It is also noted that the claim recites a cell culture medium containing at least one hyaluronic acid and lanifibranor, and does not recite requiring both hyaluronic acid and lanifibranor in the cell culture medium (see claim 10).
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
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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/JOSEPHINE GONZALES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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