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 without traverse of Group I (claims 1-6) in the reply filed on Nov. 14, 2025 is acknowledged. Claims 7-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The amended claim set filed on May 10, 2023 is being used for examination. Claims 7-14 are withdrawn. Claims 1-6 are examined below.
Priority
The instant application claims foreign priority 35 U.S.C. 119(a)-(d) to Korean Patent Application No. KR10-2020-0150504 filed on Nov. 11, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Thus, the earliest possible priority for the instant application is Nov. 11, 2020.
Information Disclosure Statement
The information disclosure statements filed May 10, 2023; Dec. 27, 2024 and Oct 30, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the examiner.
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) 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Shetty et al. (Cell Biol Interl, 2007, cited in IDS filed Dec. 27, 2024) in view of Cooper et al. (Internl J Stem Cells, 2010, cited in IDS filed on May 10, 2023).
The claims are directed to methods of culturing mesenchymal stem cells (MSCs) that include the steps of primary culturing isolated human MSCs in a medium that includes umbilical cord blood serum and subculturing the MSCs in a medium that includes fetal bovine serum (FBS).
Shetty et al. teach, “This study evaluates the feasibility of using CBS [“umbilical cord blood serum”] as a replacement for FBS for culturing MSC.” (p. 298, 2nd full para.) More specifically, Shetty et al. teach isolation of MSCs from bone marrow and teach culturing and subculturing in both FBS and CBS. (pg. 294, “2.4 Isolation and expansion of MSC”). While generally finding that CBS is a preferred alternative to FBS due to its non-xenogeneic properties, Shetty et al. teach that CBS is a comparable substitute for the early passages of MSCs, but after more than 3 passages, cells from the CBS culture “sloughed off”, not enabling MSCs cultured in CBS beyond passage 3 to have the same adherence as those passaged in FBS at this subculturing time point. (pg. 298, 2nd full para.).
Shetty et al. do not actually teach switching from CBS to FBS media for culturing MSCs after passage 3.
Cooper et al. teaching culturing and subculturing of umbilical cord derived MSCs in (1) cord blood serum (CBS) (“umbilical cord blood serum”) or (2) FBS, as “MSCs derived and expanded in cord blood serum are better suited for clinical application.” (Abstract, pg. 120, “Isolation and culture of umbilical cord mesenchymal stem cells using cord blood serum and fetal bovine serum”). Cooper et al. further teach that CBS can be more cheaply obtained than FBS. (pg. 126, 2nd col.).
It would have been obvious for one of ordinary skill in the art at the time of the invention to have modified the process of culturing bone marrow MSCs in CBS media (taught by Shetty et al.) to include changing the CBS media to FBS media when subculturing MSCs after passage 3 (“primary culturing isolated human MSCs in a medium that includes umbilical cord blood serum and subculturing the MSCs in a medium that includes FBS”) because it would have been obvious to substitute one known element for another to obtain predictable results. Making this substitution would have led to predictable results with a reasonable expectation of success because Shetty et al. teach that if using MSCs after passage 3, FBS outperforms CBS. As such, at least in an in vitro setting, this substitution would make sense such that the MSC cell line can continue to be propagated efficiently. Furthermore, as Cooper et al. reinforces, CBS is better suited for clinical applications (not having the drawbacks of being a xenogeneic medium), but with Shetty et al. teaching that cell adherence performance after passage 3 is hindered when using CBS, there would be a reason, in an in vitro setting, for a person of ordinary skill in the art to start with cheaper, non-xenogeneic CBS and then switch to FBS after passage 3 of the MSCs.
With respect to claim 2, Shetty et al. teach that the MSCs are bone marrow derived MSCs. (pg. 294, “2.4 Isolation and expansion of MSC”).
With respect to claims 2 and 3, Cooper et al. teach the MSCs are umbilical cord derived MSCs. (pg. 120, “Isolation and culture of umbilical cord mesenchymal stem cells using cord blood serum and fetal bovine serum”).
With respect to claims 4 and 5, Shetty et al. teach that 10% DBS and FBS is used in the medium. (pg. 294, “2.4 Isolation and expansion of MSC”).
Claim(s) 6 is rejected under 35 U.S.C. 103 as being unpatentable over Shetty et al. (Cell Biol Interl, 2007, cited in IDS filed Dec. 27, 2024) and Cooper et al. (Internl J Stem Cells, 2010, cited in IDS filed on May 10, 2023) as applied to claims 1-5 above, and further in view of Izadpanah et al. (Cancer Res, 2009, cited in IDS filed on May 10, 2023).
Shetty et al., as modified by Cooper et al., do not teach subculturing until 20th passage stem cells are obtained.
Izadpanah et al. teach culturing both bone marrow derived and adipose derived MSCs from humans and rhesus macaques to determine the effect of long-term in vitro culture on their cell cycle properties. (Abstract). Izadpanah et al. teach that 20% FBS was used in the medium of the bone marrow and adipose MSCs. (pgs. 2-3, “Cell Culture and Differentiation”). Izadpanah et al. further teach that human MSCs can routinely be cultured up to 20 passages. (pg. 5, “Results”, 1st para.). Izadpanah et al. teach that bone marrow MSCs go through cell cycle arrest at P20, while adipose MSCs show similar results at P25; and that telomerase activity in these cells starts declining after P10. (pg. 5, “Results”, 1st para.).
It would have been obvious for one of ordinary skill in the art at the time of the invention to have modified the process of culturing bone marrow MSCs in CBS media (taught by Shetty et al.) to include subculturing until the 20th passage stem cells are obtained because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Making this modification would have led to predictable results with a reasonable expectation of success because Shetty et al. teach that if using MSCs after passage 3, FBS outperforms CBS and Izadpanah et al. teach that P20 cells have various cell cycle alterations, making this a simple model for high throughput screening of drugs that, for example, might enhance telomerase activity in older cells.
Conclusion
No claims are allowed.
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/TERESA E KNIGHT/ Primary Examiner, Art Unit 1634