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 II (claims 20-27) in the reply filed on 1/6/2026 is acknowledged. The traversal is on the ground(s) that the cited reference, Heck et al. (US 9,695,137) do not teach the specific features of the in vitro method of Group II nor the composition of Group III obtained by the in vitro method. This is not found persuasive because the technical feature shared by all three groups has been determined PPARb/d-primed MSCs, which is shared by all groups. As this technical feature is known in the art based on Heck et al., the technical feature shared by the groups is not considered as “special” technical feature that defines a contribution over the prior art. See MPEP1893.03(d).
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-14 have been canceled, claims 15-19 and 28 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 20-27 have been considered on the merits.
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 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 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. PPRAd 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 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 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 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.
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.
Regarding claim 27 directed to the concentration of MSCs being 102 to 108 MSCs/ml, KR’441 in view of Cho et al. do not teach the limitation. However, Gaussin et al. teach that the cell concentrate for the finalized pharmaceutical composition is in 60x106 to 120x106 cells/ml (col. 9, lines 8-13), and this range is overlapping with the claimed range.
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.
Conclusion
No claims are allowed.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631