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 .
The following OA replaces the OA mailed on 8/10/2026 in order to correct the claim numbers incorrectly identified in the heading of the claim rejection. The contents of the OA remains the same.
Applicant’s amendment and response filed on 6/9/2026 has been received and entered into the case.
Claims 1-14 have been canceled, claims 29-32 are newly added, claims 15-19 and 28 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 20-27 and 29-32 have been considered on the merits. All arguments have been considered.
The claim rejection under 35 USC 103 has been withdrawn due to the instant amendment. However, the following claim rejection is newly presented to address the instant amendment.
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.
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.
Claim(s) 20-27 and 29-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over KR101881441B1 (KR’441; published on 7/24/2017; English translation attached) in view of Capozzi et al. (2013, Invest Ophthalmol), Cho et al. (2019, JCI Insight) and Gaussin et al. (US 10,086,016)
KR’441 teach a method of differentiating human bone marrow mesenchymal stem cells (hBM-MSC cells) in IDX medium and GW501516 (p.9, 3-2. PPARd analysis of inhibition of transcriptional activity). KR’441 teach that the incubation duration of hBM-MSC with GW501516 is 3 days (i.e. 72 hours). After the incubation, KR’441 teach that the cells were harvested (a step of collecting).
KR’441 do not teach the incubation duration being 20-30 hours (claim 20) or 24 hours (claims 30-32).
However, it would have been obvious to a person skilled in the art to adjust the incubation duration for hBM-MSC with GW501516 as one skilled in the art would recognize that the incubation duration is a result-effective parameter.
One skilled in the art would recognize that the teaching of KR’441 is directed to the assay of the transcriptional activity of PPARd in hBM-MSCs, and as a result, the PPARd agonist GW501516 increased ANGPLT4 and PDK4 gene (p.9, 3-2. PPRAd analysis of inhibition of transcriptional activity). While KR’441 does not teach any other treatment duration than 3 days to assay transcriptional activity of ANGPLT4, one skilled in the art would try to modify the treatment duration to determine sufficient amount of treatment to activate the transcriptional activity of ANGPLT4. Furthermore, it is known in the art that ANGPLT4 transcriptional activity is increased by only 6 hours of treatment with GW0742 for human endothelial cells before total RNA being extracted for the assay according to Capozzi et al. (see p.4198, 1st col.).
Thus, it would have been obvious to a person skilled in the art to try various different incubation time for ANGPLT4 expression in hBM-MSCs by treating with a PPARd agonist with a reasonable expectation of success. As the incubation time is from 6 hour treatment as taught by Capozzi et al. and up to 3 days as taught by KR’441, one skilled in the art would try various different time including the claimed 20-30 hours or 24 hours for activating ANGPLT4 in hBM-MSCs.
KR’441 do not particularly disclose that the hBM-MSCs were harvested in a pharmaceutically acceptable carrier without GW501516.
However, it would have been obvious to a person skilled in the art to harvest the hBM-MSCs of KR’441 with a pharmaceutically acceptable carrier for the purpose of using the hBM-MSCs in various application as desired. One skilled in the art would recognize that the teaching of KR’441 is directed to the assay of the transcriptional activity of PPARd in hBM-MSCs, and as a result, the PPARd agonist GW501516 increased ANGPLT4 and PDK4 gene (p.9, 3-2. PPRAd analysis of inhibition of transcriptional activity). As ANGPLT4 is known to possess anti-inflammatory activity and facilitates macrophage polarization to induce cardiac repair according to Cho et al. (Abstract) and allogeneic hBM-MSCs are known to be used for treating heart disease according to Gaussin et al. (see Abstract; col. 5, lines 3-19 and lines 39-44; col. 6, lines 49-57). Thus, it would have been obvious to a person skilled in the art to induce ANGPLT4 expression in hBM-MSCs by treating with a PPRAd agonist prior to the therapeutic use of hBM-MSCs in cardiac repair with a reasonable expectation of success.
Regarding the step of removing the culture medium and washing the MSCs, it is considered that the “harvesting” step taught by KR’441 inherently involves removing the culture medium. Furthermore, as discussed above, in order to formulate a pharmaceutical composition comprising hBM-MSCs for the purpose of treating in cardiac repair, one skilled in the art would recognize that the hBM-MSCs treated with a PPRAd agonist would be washed and mixed with a pharmaceutically acceptable excipient/carrier for the composition comprising hBM-MSCs with a reasonable expectation of success.
Regarding the pharmaceutically acceptable carrier of step (d) of claim 20, one skilled in the art would recognize that the hBM-MSCs treated with the PPRAd agonist, GW501516, would be formulated for therapeutic purpose, and thus, it would have been obvious to formulate the hBM-MSCs in a pharmaceutically acceptable carrier as taught by Gaussin et al. (Abstract; col.2, lines 57-62; col.4, lines 37-40).
Regarding the intended purpose of the product prepared by the claimed method for treating ischemia-reperfusion injury of claim 20, the intended purpose does not require any active step to be performed for the claimed method and thus, this limitation does not provide any weight in determining patentability of the claimed invention. Nevertheless, the combined teachings of KR’441 in view of Capozzi et al., Cho et al. and Gaussin et al. would meet the limitation as the hBM-MSCs treated with GW501516 would be utilized in treating heart disease as discussed above.
Regarding the limitation directed to the concentration of MSCs being 103 to 2x104 MSCs/ml (claim 20) or 2,500 to 10,000 MSC cells/ml (claim 27), KR’441 in view of Cho et al. do not teach the limitation.
However, it is submitted that the concentration of the MSCs for the purpose of a pharmaceutical composition is readily modified by routine experimentations. One skilled in the art would recognize that the cell concentration can be a result-effective parameter and would try to adjust as needed. Furthermore, it is well settled that routine optimization is not patentable, even if it results in significant improvements over the prior art. In support of this position, attention is directed to the decision in In re Aller, Lacey, and Haft, 105 USPQ 233 (CCPA 1955): Normally, it is to be expected that a change in temperature, or in concentration, or in both, would be an unpatentable modification. Under some circumstances, however, changes such as these may impart patentability to a process if the particular ranges claimed produce a new and unexpected result which is different in kind and not merely in degree from the results of the prior art. In re Dreyfus, 22 C.C.P.A. (Patents) 830, 73 F.2d 931,24 USPQ 52; In re Waite et al., 35 C.C.P.A. (Patents) 1117, 168 F.2d 104, 77 USPQ 586. Such ranges are termed "critical" ranges, and the applicant has the burden of proving such criticality. In re Swenson et al., 30 C.C.P.A. (Patents) 809, 132 F.2d 1020, 56 USPQ 372; In re Scherl, 33 C.C.P.A. (Patents) 1193, 156 F.2d 72, 70 USPQ 204. However, even though applicant's modification results in great improvement and utility over the prior art, it may still not be patentable if the modification was within the capabilities of one skilled in the art. In re Sola, 22 C.C.P.A. (Patents) 1313, 77 F.2d 627, 25 USPQ 433; In re Normann et al., 32 C.C.P.A. (Patents) 1248, 150 F.2d 708, 66 USPQ 308; In re Irmscher, 32 C.C.P.A. (Patents) 1259, 150 F.2d 705, 66 USPQ 314. More particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Swain et al., 33 C.C.P.A. (Patents) 1250, 156 F.2d 239, 70 USPQ 412; Minnesota Mining and Mfg. Co. v. Coe, 69 App. D.C. 217, 99 F.2d 986, 38 USPQ 213; Allen et al. v. Coe, 77 App. D. C. 324, 135 F.2d 11,57 USPQ 136. (Emphasis added). With regards to determining experimental parameters, such as time in culture, the court has held that "[d]iscovery of optimum value of result effective variable in known process is ordinarily within skill of art (In re Boesch and Slaney, 205 USPQ 215 (CCPA 1980)).
The adjustment of particular conventional working conditions (e.g., concentration) is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan having the cited reference before him/her.
Regarding claim 21 directed to the bone-marrow derived MSCs, the hBM-MSCs of KR’441 would meet the limitation.
Regarding claim 22 directed to “allogenic”, this limitation does not provide any active step of the method preparing the composition. Rather this limitation is directed to the intended use of the composition. Nevertheless, it is extremely well known in the art that allogenic MSCs are utilized in various therapeutic purpose. Furthermore, Gaussin et al. teach that the cells may be allogeneic (col. 5, lines 17-19).
Regarding claim 22 directed to the MSCs being obtained from a healthy subject, while the references do not particularly disclose that the hBM-MSCs are from healthy subjects, it would have been obvious to a person skilled in the art to use hBM-MSCs from healthy donors with a reasonable expectation of success as it is well established practice in cell therapy to use healthy cells from healthy donors.
Regarding claim 23 directed to the concentration of the PPRAd agonist, Fig. 5D and E disclose that the concentration of GW501516 is 10 mM, and this is within the claimed range.
Regarding claim 24, the PPRAd agonist of KR’441 is identical to GW501516 as discussed above.
Regarding the limitation of claim 25 directed to the culture medium does not contain a viral vector for transducing MSCs. The teaching of KR’441 does not involve any viral transduction.
Regarding claim 26 directed to the washing step being performed with a solution that does not comprise the PPRAd agonist, as discussed above, it would have been obvious to a person skilled in the art that the hBM-MSCs are harvested after the treatment with GW501516 by removing the culture medium containing GW501516 would be removed and the harvested cells are formulated by combining with a pharmaceutically acceptable excipient in order to prepare the pharmaceutical composition for administering into a subject to treat a heart disease. By doing so, one skilled in the art would recognize that the pharmaceutically acceptable carrier known in the art would not contain the PPRAd agonist.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments filed 6/9/2026 have been fully considered but they are not persuasive.
First, the instant 103 rejection has been modified to address newly added limitation and cites a new reference.
Applicant argued that KR’441 (Shin) teaches a method using MSCs and PPARd agonist or PPARd antagonist as reference products to test the activity of the new compound discovered by Shin. It is acknowledged that Sin is directed to the compound for treating diseases associated with abnormal adiponectin levels. However, Shin also teaches a method comprising providing MSCs, incubating (cultivating) MSCs in a culture medium comprising a PPARb/d agonist. These are steps claimed in the instant application. The purpose of the Shin’s method is to assay the transcriptional activity of ANGPLT4 as discussed in the claim rejection. Regardless the intended purpose, the method steps taught by Shin read on the claimed steps. Regarding the teachings of Cho, applicant stated that Cho provides motivation to use soluble factors such as ANGPTL4 instead of stem cells for safe and effective therapy. While Cho states that capability of ANGPTL4 to induce tissue repair is a promising opportunity for safe stem-cell-free regeneration therapy, the teaching of Cho is in fact directed to elucidate the mechanism of MSCs in their contribution to the anti-inflammatory activity for cardiac repair. Cho’s teaching provides that ANGPTL4 is a player responsible for the anti-inflammatory activity of MSCs. Based on this teaching, one skilled in the art recognize that the treatment of MSCs with PPARb/d agonist taught by Shin renders the cells more suitable for tissue repair as the MSCs are activated to produce ANGPTL4.
Regarding the incubation duration as amended, Shin (KR’441) does not teach the claimed duration for treating MSCs with PPARb/d agonist. However, as newly discussed in the claim rejection above, it is known in the art that activation of transcription of ANGPTL4 can be as short as 6 hours according to Capozzi et al. Thus, one skilled in the art would try to adjust the duration of treating the MSCs taught by Shin for activating transcriptional activity of ANGPTL4 in MSCs.
Regarding the newly added limitation directed to the concentration of MSCs, applicant alleged that Examples of the instant application provide evidence that the concentration of MSCs ranging from 1,000 to 20,000 cells/ml is optimal for a cardioprotective effect. It is acknowledged that the instant specification discloses examples showing the concentration as claimed being used in a specific administration protocol. According to the instant specification, MSC perfusion was carried out during the reperfusion to the heart after ischemia. It is understood that the claimed cell concentration is particularly adapted for perfusion, and for the method of treating ischemia-reperfusion injury. While the instant claims disclose the intended purpose of the cells, however, the method is directed to the preparation of the cells not the use of the prepared cells, and there is no active step of using the primed cells for the ischemia-reperfusion injury. Thus, it is the Examiner’s position that the claimed method is obvious over the combined teachings of the cited references, particularly in the absence of criticality for the claimed cell concentration in making a composition. As the cell concentration appears to be significant for the method of treating, applicant is advised to add a step of administering the collected cells at the claimed concentration to the procedure disclosed in the instant specification (e.g. Fig. 1A).
Conclusion
No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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