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. Examiner’s Comment The Examiner of Record has changed for the instant Application. The new Examiner is BRENDAN THOMAS TINSLEY. Contact information can be found at the bottom of this action. It is noted that throughout this Official Action, where reference is made to the Instant Specification, the Examiner will be referring to the publication of the Instant Application (US2023/0330151). Election/Restrictions Applicant's election with traverse of the invention of group II, drawn to a method of promoting differentiation of neural stem cells into dopaminergic neurons in the reply filed on 22 October, 2025 is acknowledged. The traversal is on the grounds that (1) there would not be a serious burden on the Examiner and invokes MPEP § 803, and (2) unity of invention is present and that the description needs to be taken into account. This is not found persuasive for the following reasons: Applicant argues that there would not be a serious burden on the Examiner and invokes MPEP § 803. This is not found persuasive because the instantly filed application was filed under 37 CFR 371. As stated in 1893.03(d), unity of invention (not restriction) practice is applicable in such cases. Search burden is not a criteria in 371 cases. Further, e ach application is reviewed on its own merits (see in re Giolito and Hoffman , 188 USPQ 645). Whether the international examiner found lack of unity cannot be parsed in this case. What is critical is whether the lack of unity is correct in the instant case. Applicant argues that unity of invention is present and that the description needs to be taken into account. This is not found persuasive because Applicant has not actually argued against the references applied to break unity of invention. Further, while the claims are to be read in light of the description, it is improper to import limitations from the specification into the claims (in either case irrelevant because Applicant has not pointed to anywhere in the specification in their arguments). Even further, it is noted that the inventions of groups I and II share the composition as a technical feature (not a special technical feature, see Restriction Requirement, 22 August, 2025) while the inventions of groups III-VI share only the technical feature of a dopaminergic neuron (also not a special technical feature as disclosed by Sook et al.). The requirement is still deemed proper and is therefore made FINAL. Claims 1-7, and 12-15 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. Therefore, claims 8-11 are pending and under examination in the instant Official Action. Priority The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/ KR2021/011263 , filed 24 August , 202 1 , which claims priority to Republic of Korea Application No s . KR10-2021-0111440 , filed 24 August , 20 21, and KR10-2020-0106224, filed 24 August, 2020 . Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified untranslated copies of papers required by 37 CFR 1.55 have been filed in this application on 23 February, 2023 . Applicant cannot rely upon the foreign priority papers to establish the effective filing date based upon these documents because a translation of said papers has not been made of record in accordance with 37 CFR 1.55. See MPEP § 201.15. The earliest possible priority for the instant application is 24 August, 202 1 . Information Disclosure Statement The information disclosure statement (IDS) submitted on 20 June, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Drawings The Drawings submitted on 24 May, 2023 are accepted by the Examiner. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(b): (b ) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the appl icant regards as his invention. Claims 8-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 8 recites “a medium comprising fusaric acid, ascorbic acid, nicotinamide adenine dinucleotide (NAD+), or a combination thereof”. This recitation is indefinite because it is unclear what “or combinations thereof” encompasses. It is unclear whether Applicant intends the scope of claim 8 to encompass fusaric acid, ascorbic acid, or NAD+ individually or any of the three in any combination or whether Applicant intends the scope to encompass fusaric acid, ascorbic acid, or NAD+ individually or all three together. It is noted that the instant specification teaches fusaric acid, fusaric acid and ascorbic acid, fusaric acid and NAD+ and fusaric acid, ascorbic acid and NAD+ together (Specification, [0085]). Claim 11 appears to be directed to a medium comprising all three of fusaric acid, ascorbic acid and NAD+ but this is strained insofar as claim 11 depends from claim 8 which has several conflicting interpretations. Accordingly, a person having ordinary skill in the art would not be apprised of the scope of the claimed invention and claim 8 is indefinite. Claims 9-11 are further rejected for their dependency on a rejected base claim. Claim 8 recites “subculturing neural stem cells”. This recitation is unclear because the claim does not require a culture of neural stem cells from which one might subculture. Consequently, it is unclear from where the neural stem cells are subcultured and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought. The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 8-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 8 broadly encompasses a method of promoting differentiation of neural stem cells into dopaminergic neurons, comprising culturing the neural stem cells in a medium comprising any amount of any combination of fusaric acid, ascorbic acid, and NAD+ or either individually (applying the broadest reasonable interpretation, see 112(b) above). None of claims 9-10 further limit the scope of the medium of claim 8. The working examples teach the isolation of neural stem and progenitor cells (NSPCs) from fetal midbrains (FM-NPSCs) ([0081]-[0084]). The working examples then teach the differentiation of these FM-NSPCs for 6 days in medium comprising (1) 0.1 millimolar (mM) fusaric acid, (2) 0.1mM fusaric acid and 0.2 micromolar ( μ M) acetic acid, (3) 0.1mM fusaric acid and 1mM nicotinamide adenine dinucleotide (NAD+), or (4) 0.1mM fusaric acid, 0.2 μΜ ascorbic acid, and 1 m Μ NAD+ ([0085]-[0086]). The working examples teach cells with increased tyrosine hydroxylase (TH) expression (evaluated with fluorescence microscopy (see Figures)) as the result of this differentiation and teach TH expression as a marker of dopaminergic neurons ([0086]). The working examples teach that the differentiation of FM-NSPCs into TH+ cells did not differ between cells cultured in fusaric acid and cells cultured with fusaric acid with ascorbic acid and NAD+ when the FM-NSPCs were subcultured prior to differentiation for less than 10 days (FIG. 11A, [0098]) whereas those subcultured for more than 10 days then cultured with fusaric acid, ascorbic acid, and NAD+ were significantly more TH+ (FIG. 11B and C, [0099]). Finally, the working examples teach that “even when [ascorbic acid] or NAD+ was further added, respectively, than when [fusaric acid] was added alone, there was no significant effect on an ability of the neural stem cells isolated from a late stage subculture to differentiate into dopaminergic neurons” ([0093]). Thus, the working examples only teach combinations which comprise fusaric acid and they teach unpredictability with respect to promoting differentiation of NSPCs into dopaminergic neurons depending on how many times the NSPCs are subcultured prior to differentiation and the particular combination employed (all of which include fusaric acid) . A skilled artisan at the time of filing knew that methods for the differentiation of neural stem cells into dopaminergic neurons in vitro typically did not include a medium supplemented with NAD+ as evidenced by the relative lack of teachings in the art at the time of filing. Further, the exposure of NSPCs to 1mM NAD+ (the exact amount used by Applicants) is known to inhibit the morphological development of neurons differentiated from the NSPCs ( Huang et al. Cells 11.8 (2022): 1283 , hereinafter “Huang”, page 12, “Conclusions”) . Thus, there is unpredictability in the field of dopaminergic neuron differentiation from NSPCs with respect to NAD+ supplementation. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021). Further, A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem , 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). See MPEP 2163(II)(A)(3)(a)(ii). In this case, the specification teaches only media comprising fusaric acid alone at 0.1mM , 0.1mM fusaric acid with 0.2 μ M ascorbic acid, 0.1mM fusaric acid with 1mM NAD+, or 0.1mM fusaric acid with 0.2 μΜ ascorbic acid and 1 m Μ NAD+. There is no discussion of media with ascorbic acid or NAD+ alone or in combination without fusaric acid or of any other concentrations of each of the ingredients . Therefore, Applicant has not disclosed a sufficient number of species for a skilled artisan to conclude that they had possession of the invention claimed. Claim Rejections - 35 USC § 102 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale , or otherwise available to the public before the effective filing date of the claimed invention. Claims 8-10 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by US2013/0089926 (hereinafter “Moon” , OF RECORD in the IDS submitted: 20 June, 2023 ) . Moon discloses a method for differentiating human neural progenitor cells into dopaminergic neurons comprising culturing human neural progenitor cells in a medium comprising fusaric acid (Moon, [0031]). Moon specifically discloses to subculture the hNPCs before differentiation (Moon, [0023]-[0026], FIG. 7-10). Therefore, Moon discloses all of the limitations of instant claim 8. Regarding claims 9-10, Moon specifically discloses subculture for 7, 11, or 17 passages and teaches increased TH+/Tuj1+ cells from 11 and 17 passages compared to just 7 passages (Moon, FIG. 7, [0023]). Thus, Moon teaches to subculture more than ten and less than 20 times. 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. 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 8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over US2013/0089926 (hereinafter “Moon”, OF RECORD in the IDS submitted: 20 June, 2023) in view of Rharass et al. Journal of Biomedical Science 24.1 (2017): 78 , hereinafter “ Rharass ”, and Fricker, et al. International Journal of Tryptophan Research 11 (2018): 1178646918776658 , hereinafter “Fricker” . Moon discloses a method for differentiating human neural progenitor cells into dopaminergic neurons comprising culturing human neural progenitor cells in a medium comprising fusaric acid (Moon, [0031]). Moon specifically discloses to subculture the hNPCs before differentiation (Moon, [0023]-[0026], FIG. 7-10). Therefore, Moon discloses all of the limitations of instant claim 8. Moon does not teach to add ascorbic acid or NAD+ to the culture medium. Rharass teaches dopaminergic neurons differentiated from neural progenitors as a therapy for neurodegenerative diseases and teaches that ascorbic acid is an essential nutrient that enhances dopamine neuron conversion from pluripotent cells ( Rharass , “Background”, first paragraph). Rharass specifically teaches a medium supplemented with ascorbic acid for the culturing of neural progenitor cells ( Rharass , “Cell Culture” and “Cell Treatment” headings). Rharass teaches that ascorbic acid treatment of neural progenitor cells has a pro-oxidant effect which enhances the expression of genes which stimulate cell commitment decisions and improves the neuronal yield of in vitro cultured neural progenitor cells to a level necessary for regenerative therapies ( Rharass , “Conclusions”). Thus, a person having ordinary skill in the art would have been motivated by Rharass to have added ascorbic acid to the culture medium of Moon to improve the neuronal yield of in vitro cultured neural progenitor cells. Fricker teaches that nicotinamide has long been associated with neuronal development, survival, and function (Fricker, Abstract). Fricker also teaches that nicotinamide has a neuroprotective effect in neurodegenerative conditions like Alzheimer’s, Parkinson’s, and Huntington’s disease (Fricker, Abstract). Fricker teaches that nicotinamide is a key component of the metabolic pathway involved in the production of NAD+ (Fricker, page 1, fourth paragraph). Fricker also teaches that supplementation with nicotinamide increases NAD+ through downregulation of poly(ADP-ribose) polymerases (PARP) which results in a neuroprotective effect (Fricker, page 7, second through fourth paragraphs). Thus, Fricker suggests to a person having ordinary skill in the art t hat NAD+ has a neuroprotective effect on neurons and that its supplementation through NAD+ itself or its precursor, nicotinamide, can have this neuroprotective effect. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have added ascorbic acid and NAD+ to the medium of Moon and to have arrived at the invention claimed in instant claim 11 with a reasonable expectation of success because they would have been motivated to do so to improve the neuronal yield of in vitro cultured neural progenitor cells as taught by Rharass and because Fricker suggests to supplement NAD+ for its neuroprotective effects. There would have been a reasonable expectation of success in adding ascorbic acid and NAD+ to the medium of Moon insofar as Rharass and Fricker teach reasonable beneficial effects of each ingredient on neuronal differentiation and proliferation. 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. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer . Claims 8-1 1 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1-9 of U.S. Patent No. 8,921,107 . Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims are a species of the instant claims and limitations not explicitly taught by the patent are taught or suggested by Rharass et al. Journal of Biomedical Science 24.1 (2017): 78 , hereinafter “ Rharass ”, and Fricker, et al. International Journal of Tryptophan Research 11 (2018): 1178646918776658 , hereinafter “Fricker” . Patented claim 1 reads “A method for differentiating human neural progenitor cells into dopaminergic neurons, which comprises culturing human neural progenitor cells in a medium comprising fusaric acid”. Pending claim 8 reads “ A method of promoting differentiation of neural stem cells into dopaminergic cells, comprising: subculturing neural stem cells; and differentiating the subcultured neural stem cells in a medium comprising fusaric acid, ascorbic acid, nicotinamide adenine dinucleotide (NAD+), or a combination thereof. ” Pending claim 8 is narrower than patented claim 1 insofar as pending claim 8 required “subculturing”. Note that MPEP 804(II)(2)(a) sets forth instances where it is acceptable to utilize the disclosure of a U.S. patent document in conjunction with its claims for ODP rejections. In particular, the MPEP notes that the portion of the specification that supports the patent claims may be considered. The court in AbbVie Inc. v. Kennedy Institute of Rheumatology Trust pointed out that “this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.” In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014). The court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003). The patent specification specifically discloses the subculture of NPCs before differentiating them with a medium comprising fusaric acid and specifically teaches 7, 11, or 17 passages as required by pending claims 9-10 (col. 3, lines 35-56). Thus, pending claims 8-10 are an obvious variant of the invention of patented claims 1-9. With regard to the limitation of pending claim 11, Rharass and Fricker teach and suggest respectively to add ascorbic acid and NAD+ to the medium (See above 103 rejection). Therefore, claim 11 would have been obvious over the patented claims in view of Rharass and Fricker. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT BRENDAN THOMAS TINSLEY whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-5906 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Mon-Fri 8:00-5:00 . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT MARIA G LEAVITT can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-1085 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /BRENDAN THOMAS TINSLEY/ Examiner, Art Unit 1634 /MARIA MARVICH/ Primary Examiner, Art Unit 1634