DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office Action is in response to the paper filed 9 February 2026. Claims 1 and 11 have been amended. Claims 12 and 13 have been cancelled. Claims 1, 4-7, 9, and 11 are currently pending and under examination.
This Application is a § 371 U.S. national stage of International Application No. PCT/KR2020/011248, filed August 24, 2020, which claims priority to Korean Patent Application No. 10-2019-0103217, filed August 22, 2019.
Withdrawal of Rejections:
The rejection of claims 1, 4-7, 9, and 11-13 under 35 U.S.C. 103 as being unpatentable over Park et al., in view of Brodie et al., as evidenced by Son et al., is withdrawn.
New Rejections Necessitated by Amendment:
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.
Claims 1, 4-7, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (Human Mesenchymal Stem Cell-Derived Schwann Cell-Like Cells Exhibit Neurotrophic Effects, Via Distinct Growth Factor Production, in a model of Spinal Cord Injury, Glia, Vol. 58, (2010), pp. 1118-1132 – Previously Presented), in view of Hantash et al. (US 2017/0065639; Published 2017), as evidenced by Son et al. (IDS; Glia-Like Cells from Late-Passage Human MSCs Protect Against Ischemic Stroke Through IGFBP-4, Molecular Neurobiology, Vol. 56: 7617- 7630, 2019 – Previously Presented).
With regard to claims 1 and 11, Park et al. teach a method of treating CNS injury by administering Schwann cell-like cells (Abs.). The Schwann cell-like cells, which are glia-like cells, are differentiated from human mesenchymal stem cells (hMSCs) (Abs.; p. 1119, Left Col., Materials and Methods, Cell Culture, line 1-2). The method including obtaining hMSCs passaged 4-12 times (Abs.; p. 1119, Left Col., Materials and Methods, Cell Culture, line 1-2).
Then, the passaged hMSCs are cultured for 24 hours in growth medium which contains DMEM and 10% FBS, with 1 mM β-mercaptoethanol (p. 1119, Left Col., Materials and Methods, Cell Culture, line 1-6; SC Induction of hMSCs, line 1-3). After that, the passaged hMSCs are cultured for 3 days (72 hours) in growth medium which contains DMEM and 10% FBS, with 0.28 µg/mL all-trans-retinoic acid (trentinoin) (p. 1119, Left Col., Materials and Methods, Cell Culture, line 1-6; SC Induction of hMSCs, line 3-4). Finally, the passaged hMSCs are cultured for 8 days in growth medium which contains DMEM and 10% FBS, with 10µM forskolin, 10 ng/mL bFGF, 5 ng/mL PDGF-AA, and 200 ng/mL HRG-β1 (p. 1119, Left Col., Materials and Methods, Cell Culture, line 1-6; SC Induction of hMSCs, line 5-8).
It is noted that the process as taught by Park et al. produces the glia-like cells as used in the claimed method (see evidentiary reference Son et al., p. 7618, Right Col., Glia-Like Cell Induction of hMSCs (ghMSCs), para. 1: indicates that glia-like cells were induced from hMSCs according to the protocol of Park et al.), wherein the cells produced by this method comprise oligodendrocytes, astrocytes, microglia, and radial glial cells, and express insulin-like growth factor binding protein (IGFBP)-4 and pregnancy-associated plasma protein (PAPP)-A (see evidentiary reference Son et al.: Fig. 1b, p. 7624, Left Col., Results, Induction of Late-Passage hMSCs into Glia-Like Cells, Para. 2, through Right Col., Para. 2).
It is not specifically taught that the glia-like cells are administered for treating Alzheimer’s disease, or that the hMSCs are passaged 13 to 15 times.
Hantash et al. teach that human MSCs can be maintained in vitro under non-differentiating conditions for a number of passages, including for at least 10 passages, at least 15 passages, or at least 20 passages, before being induced to differentiate to a desired cell type (Para. 31, 75, 77, 78, 81). An ordinary artisan would have been motivated from the teachings of Hantash et al. to passage hMSCs a number of times including 12-15 passages, with is fully encompassed within the expressly taught range of at least 10. The cells passaged as taught are usable to treat degenerative diseases including Alzheimer’s disease and dementia (Para. 89).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Park et al. and Hantash et al., because both teach the late passaging of hMSCs and their subsequent differentiation and use for treatment of neurological disorders. It is known in the art as taught by Hantash et al. that hMSCs may be passaged for at least 10 passages, even including over 15 or 20 passages, before being induced to differentiate to a desired cell type, where cells passaged as taught are usable to treat neurological diseases including Alzheimer’s disease and dementia. It would have been obvious to one of ordinary skill in the art that hMSCs of Park et al. may be passaged for more than 12 passages, including for 13-15 passages, as Hantash et al. teach that hMSCs passaged as such may be successfully differentiated and used for treatment of neurological diseases. Additionally, an ordinary artisan would have been motivated to administer the glia-like cells as taught by Park et al. to a subject with Alzheimer’s disease as taught by Hantash et al., to predictably improve the method of Park et al., by providing treatment for an additional neurological disorder. Thus, rendering the method of Park et al. more useful for a wider population.
Taken together, Park et al. and Hantash et al. render obvious the method as claimed, including the components as claimed. As such, the results of improving memory and spatial cognitive ability of the subject as compared to a control subject not administered the ghMSCs, would naturally flow from performance of the combined method of Park et al. and Hantash et al.
With regard to claim 4, Park et al. teach that the glia-like cells are derived from bone marrow (Abs.).
With regard to claims 5-7, taken together, Park et al. and Hantash et al. render obvious the method as claimed, including the components as claimed. As the components cannot be separated from their properties, and as the results naturally flow from performance of the method as rendered obvious, the results that the method reduces expression of an inflammasome factor including NLRP3, caspase-1, or IL-1 in neural stem cells in the subject as compared to a control from a subject not administered glia-like cells; enhances hippocampus-dependent spatial learning ability in the subject as compared to a control from a subject not administered glia-like cells; and improves spatial cognitive ability in the subject as compared to a control from a subject not administered glia-like cells, would necessarily flow from performing the method of Park et al. and Hantash et al.
With regard to claim 9, Park et al. teach that N2a cells are plated at 1.3 x 105 cells/well and glia-like cells are placed at 5 x 104 cells/insert (p. 1120, Left Col., Coculture of Neuro2A Cells and hMSCs; Fig. 5A). Additionally, it is taught that 3 x 104 glia-like cells cells/1.5µL are transplanted onto the ventral region of each spinal cord slice for treatment (p. 1120, Right Col., hMSC Transplantation into the Lysolecithin-Treated Spinal Cord Slice Culture, para. 1 to p. 1121, Left Col., para. 1).
While it is not specifically taught by Park et al. or Hantash et al. that 6 x 105 to about 6 x 107 cells/kg body weight of the subject are administered, it would have been routine for one of ordinary skill in the art to determine the optimal dosage of the glia-like cells based known parameters such as age, condition, sex, disease severity, frequency of doses, and route of administration to treat Alzheimer’s disease as desired based on the specific patient’s characteristics. Additionally, please also note that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the dosage administered, including from 6 x 105 to about 6 x 107 cells/kg body weight of the subject, to result in the administration of an effective amount of the glia-like cells to treat Alzheimer’s disease in the specific patient.
Response to Arguments
Applicant’s arguments relate to the combination of Park et al. and Brodie et al., which has been withdrawn in view of Applicant’s amendments. Therefore, these arguments are moot. However, new rejections are set forth above.
Conclusion
No claims are allowable.
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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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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