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 26 May 2026. Claims 1, 6, 57, and 58 have been amended. Claims 1, 2, 6, 12, 14, 57, and 58 are currently pending and under examination.
This application is a Continuation of International Patent Application No. PCT/US2020/030703, filed April 30, 2020, which claims priority to U.S. Provisional Patent Application No. 62/840,956, filed April 30, 2019.
Withdrawal of Rejections:
The rejection of claims 1, 2, 6, 12, 14, 57, and 58 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn.
Maintenance/Modification of 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, 2, 6, 12, 14, 57, and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Finley et al. (IDS; US 2017/0022475, Published 2017), as evidenced by ATCC (Eagle's Minimum Essential Medium (EMEM), 2024, Available online at: www.atcc.org/products/30-2003).
With regard to claims 1 and 6, Finley et al. teach a method of selectively enriching pluripotent cells in a mixed population of cells that includes non-pluripotent cells, the method comprising culturing the mixed cell population in a culture medium that has no exogenous glutamine added and is glutamine-free (Para. 26-29, 31). The pluripotent cells are sorted/selected from other cells types in the mixed population, because the pluripotent cells survive the glutamine deprivation, while the other cell types in the mixed population do not (Para. 28-29). The mixed cell population including the pluripotent cells is cultured in the glutamine-free medium for time periods including 4 hours, 24 hours, or 48 hours (Para. 36-37), which are fully encompassed within 4 to 48 hours, and include about 24 hours. Additionally, it would have been obvious to one of ordinary skill in the art to utilize a culture time as taught by Finley et al. for culturing the taught mixed cell populations in glutamine-free media.
Finley et al. further teach that maintenance media for embryonic stem cells, which are pluripotent cells, is supplemented with 2 mM L-glutamine (Para. 139). It is further taught that pluripotent cells can be maintained and expanded in culture media, including Eagle’s Minimum Essential Medium® (EMEM) (Para. 104), which has 2 mM L-glutamine (see ATCC, Formulation), and is a complete medium. Additionally, media such as Dulbecco's Modified Eagle's Medium® (DMEM), DMEM F12 Medium®, F-12K Medium®, Iscove’s Modified Dulbecco's Medium®, and RPMI-1640 Medium® may likewise be utilized, and may be further supplemented with amino acids including L-glutamine (Para. 104).
As noted above, Finley et al. teach enriching pluripotent cells in a mixed population of cells including non-pluripotent cells by culturing the mixed population in glutamine-free media, which eliminates the other cell types from the mixed population, and Finley et al. also teach that stem cells can be maintained and expanded in culture media containing glutamine. As such, it would have been obvious to one of ordinary skill in the art to maintain and expand the enriched pluripotent stem cells left after sorting using the glutamine-free medium, in the taught glutamine-containing media, to maintain and expand the stem cells that were desirably obtained from sorting the mixed cell population.
With regard to claim 2, Finley et al. teach that the pluripotent cells are self-renewing pluripotent cells, such as pluripotent stem cells (Para. 78).
With regard to claims 12 and 14, Finley et al. render obvious the method as claimed, including all components as claimed. As the components cannot be separated from their properties, and the method cannot be separated from its results, practicing the method as rendered obvious by Finley et al. would necessarily provide the results that the pluripotent cells in the cell population are increased between about 10% to about 500% as compared to pluripotent cells in a cell population that has not been cultured in the glutamine-free medium; and the pluripotent cells have an elevated cellular αKG/succinate ratio as compared to the non-pluripotent cells and/or a higher level of Nanog, Oct4, Sox2, Esrrb, Zfp42, Klf4, Tfcp211, Stat3, or combinations thereof as compared to the non-pluripotent cells.
With regard to claims 57 and 58, Finley et al. teach the culturing of pluripotent cells in glutamine-free and glutamine-containing media as discussed previously, and also teach cell culture times that include 24 and 48 hours (see Para. 33, 37, 39, 141, 143, 158, 159). It would have been routine for one of ordinary skill in the art to determine the most appropriate time for culturing the pluripotent cells in the glutamine-containing maintenance/expansion media based on the desired end use of the pluripotent cells that were sorted and expanded. 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 culture time for the sorted pluripotent cells in the glutamine-containing maintenance/expansion media, including to at least 24 hours or 48 hours, to result in sorted pluripotent cells that have been expanded to a desired amount when practicing the taught method.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1, 2, 6, 12, 14, 57, and 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-6 and the disclosure of U.S. Patent No. 11,203,739. Although the claims at issue are not identical, they are not patentably distinct from each other because both encompass methods for selectively enriching pluripotent cells, including self-renewing pluripotent cells, in a cell population comprising non-pluripotent cells and the pluripotent cells, wherein the method comprises culturing the cell population in a substantially glutamine-free medium, which encompasses a glutamine-free medium, for a sufficient amount of time, including 4 hours or 24 hours, which is between 4 to 48 hours, and includes about 24 hours, to provide the selectively enriched pluripotent cells; and maintaining and expanding the enriched pluripotent stem cells in the cell population in complete media containing glutamine, wherein maintenance culture time periods including at least 24 or 48 hours would have been obvious to utilize, as these culture times are specifically recited (Instant claims: 1, 2, 6, 57, 58; Cited patent claims: 1, 3-6; Col. 7, line 4-6; Col. 21, line 56 to Col. 22, line 25; Col. 30, line 22-33). Wherein as the components of each method cannot be separated from their properties, and the method cannot be separated from its results, practicing the method as rendered obvious by both the instant claims and cited patent claims and disclosure would necessarily provide the results that the pluripotent cells in the cell population are increased between about 10% to about 500% as compared to pluripotent cells in a cell population that has not been cultured in the glutamine-free medium; and the pluripotent cells have an elevated cellular αKG/succinate ratio as compared to the non-pluripotent cells and/or a higher level of Nanog, Oct4, Sox2, Esrrb, Zfp42, Klf4, Tfcp211, Stat3, or combinations thereof as compared to the non-pluripotent cells (Instant claims: 12, 14; Cited patent claims: 1).
Response to Arguments
Applicant urges that Finley et al. do not teach transient glutamine deprivation, where the cells are cultured in glutamine-containing media following glutamine-free culturing. Further, the unexpected properties provided by the claimed method including not requiring treatment of the stem cells with MEK and GSK3β inhibitors, is advantageous over Finley. The nonstatutory double patenting rejection is improper for the same reasons.
Applicant’s arguments have been fully considered, but have not been found persuasive.
With regard to Applicant’s argument that Finley et al. do not teach transient glutamine deprivation, where the cells are cultured in glutamine-containing media following glutamine-free culturing; as noted above, Finley et al. teach enriching pluripotent cells in a mixed population of cells including non-pluripotent cells by culturing the mixed population in glutamine-free media, which eliminates the other cell types from the mixed population, and Finley et al. also teach that stem cells can be maintained and expanded in culture media containing glutamine. As such, it would have been obvious to one of ordinary skill in the art to maintain and expand the enriched pluripotent stem cells left after sorting using the glutamine-free medium, in the taught glutamine-containing media, to maintain and expand the stem cells that were desirably obtained from sorting the mixed cell population.
With regard to Applicant’s argument about unexpected results, it is noted that conditions cited for providing the unexpected results in the specification include unclaimed limitations, such as using specifically reprogrammed mouse embryonic fibroblasts. Further, it is noted that no limitation precluding the presence of MEK and GSK3β inhibitors is included in the claims.
With regard to Applicant’s argument about the nonstatutory double patenting rejection, the suggested deficiencies of Finley et al. have been addressed 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER M.H. TICHY whose telephone number is (571)272-3274. The examiner can normally be reached Monday-Thursday, 9:00am-7:00pm ET.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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