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 .
Status of the Claims
Applicant’s submission filed 23 December 2025 has been entered. Claims 1-2, 4, 6, and 8-11 are pending. Claims 1, 4, 6, and 11 have been amended, while claims 3, 5, and 7 have been cancelled without prejudice or disclaimer. Therefore, prosecution on the merits continues for claims 1-2, 4, 6, and 8-11. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Objection to claim 5
The cancellation of claim 5 renders the objection of record moot. Therefore, the objection is withdrawn.
RE: Rejection of claims 5-6 and 11 under 35 USC 112(b)
The cancellation of claim 5 renders the rejection moot for that claim. For the remaining claims, Applicant’s amendments obviate the rejections of record.
Therefore, the rejections are withdrawn.
RE: Rejection of claims 9-11 under 35 USC 101
Applicant’s amendments to the method of independent claim 1 requiring the upregulation of
SOX9, NFIA, and NFIB to be via the introduction of a vector containing nucleic acids encoding the transcriptions factors alters the effect of the product-by-process limitation, thus obviating the rejection of record in regards to instant claims 9-10. Furthermore, Applicant’s amendments to instant claim 11 remove the “use” claim language, thereby obviating the rejection of record.
Therefore, the rejections are withdrawn.
RE: Rejection of claims 1-3, 5-9, and 11 under 35 USC 102(a)(1) over Li et al
The cancellation of claims 3, 5, and 7 renders the rejection moot for those claims. For the remaining claims, Applicant has traversed the rejection, asserting in Page 6 of the Remarks filed 23 December 2025 that Li et al do not disclose a vector that comprises base sequences encoding SOX9, NFIA, or NFIB since the vector of Li et al is a gRNA vector. In response, the Examiner respectfully submits that the broadest reasonable interpretation of the claims does not require full-length sequences encoding each of SOX9, NFIA, and NFIB. More specifically, the instant disclosure states that the sequences are not required to have 100% sequence identity to exemplary NCBI accession numbers so long as they have the activity of inducing the differentiation of human pluripotent stem cells into astrocyte-like cells. See, for example, Paragraphs [0032]-[0033] of the instant Specification filed 02 March 2023. However, the Examiner agrees with Applicant’s assertion that the gRNA vector of Li et al does not read on the claims as written, as the gRNA sequences comprised within the disclosure of Li et al do not encode functional SOX9, NFIA, and NFIB transgenes themselves.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1-4 and 7-11 under 35 USC 102(a)(2) over Ahlenius et al
The cancellation of claims 3 and 7 renders the rejection moot for those claims. For the remaining claims, Applicant's amendments to independent claim 1 requiring the limitations of previous claims 3, 5, and 7 obviate the rejection of record, as previous claim 5 was not included within the rejection of record.
Therefore, the rejection is withdrawn.
New Grounds of Rejection
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.
Claims 1-2, 4, 6, and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Ahlenius et al (US 2022/0333070 A1, of record) in view of Woodard et al (Trends Biotechnol, 2015).
Ahlenius et al is considered prior art under 35 USC 102(a)(2), with an effective filing date of 16 August 2019. Woodard et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 1, 6, and 9: Ahlenius et al disclose a method of producing induced functional astrocytes (iAs) from human pluripotent stem cells (Abstract).
As such, Ahlenius et al disclose that the human pluripotent stem cells are transfected with a combination of viral vectors capable of expressing SOX9, NFIA, and/or NFIB, which results in the overexpression of SOX9, NFIA, and NFIB in the human pluripotent stem cells (Paragraphs [0002]-[0003], [0007], [0021]-[0024], [0030], [0047]-[0048]; Figures 1, 3-4). Ahlenius et al further disclose that the transfected human pluripotent stem cells are subsequently differentiated into iAs (Paragraphs [0021]-[0024], [0034]).
Ahlenius et al further disclose that any expression vector system that is operable within the cells that are in the astrocyte differentiation pathway may be utilized (Paragraphs [0022]-[0023]).
Ahlenius et al do not disclose that the nucleic acid sequences encoding each of SOX9, NFIA, and NFIB are comprised within a single vector and separated by separator sequences, nor that abundances of SOX9, NFIA, and NFIB in the human pluripotent stem cells satisfy 1:1:1 in terms of molar ratio, as required by instant claim 1.
Woodard et al, however, disclose the insertion of a piggyBac transposon vector comprising four transcription factors each separated by a 2A protease cleavage sequence into mammalian cells for the generation of iPSCs via the differentiation of the mammalian cells (Pages 3-5, 9, 16; Figure 2). Woodard et al further disclose that the use of a single vector comprising the four transgenes allowed for better control of the copy number in the genome compared to the retroviral insertion of four separate vectors that yielded variable copy numbers (Page 4).
Woodard et al further disclose that the iPSCs can be further modified using piggyBac transposon vectors (Pages 3-4; Figure 1).
Therefore, it would have been prima facie obvious to have modified the method of Ahlenius et al such that the SOX9, NFIA, and NFIB transgenes were comprised within a single piggyBac transposon vector, as suggested in Woodard et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to utilize the piggyBac transposon vector system, as it allows for the stable transfection of the transgenes within the cells and enhanced control over the copy number when compared to the separate retroviral transduction of the transcription factors (Woodard et al: Pages 3-5; Table 1). Furthermore, the ordinary artisan would have had a reasonable expectation of success given that the piggyBac transposon vector can be utilized within iPSCs, which are cells that are in the astrocyte differentiation pathway. See MPEP § 2143(I)(G).
Consequently, Ahlenius et al in view of Woodard et al render obvious a method of producing induced functional astrocytes (iAs) from human pluripotent stem cells, wherein the human pluripotent stem cells are transfected with a piggyBac transposon vector (claim 6) comprising SOX9, NFIA, and NFIB base sequences linked together by 2A protease cleavage separator sequences, which results in the overexpression of SOX9, NFIA, and NFIB in the human pluripotent stem cells, and are then subsequently differentiated into iAs. Since the transposon vector rendered obvious by Ahlenius et al in view of Woodard et al follows the “F1-S1-F2-S2-F3 …” formula, and the copy number in the genome is highly controlled such that it would have been prima facie obvious to adjust the expression levels of SOX9, NFIA, and NFIB to 1:1:1 in terms of molar ratio, this therefore renders obvious the method of instant claim 1 and resulting astrocyte-like cells of instant claim 9. See MPEP § 2144.05 and Paragraph [0042] of the instant Specification filed 02 March 2023.
Regarding claims 2 and 11: Following the discussion of claim 1, Ahlenius et al further disclose that the human pluripotent stem cells are cultured in culture medium comprising basic fibroblast growth factor (claim 11) (Paragraphs [0071], [0114], [0138]-[0148]). This therefore reads on the method of instant claim 2.
Regarding claim 4: Following the discussion of claim 1, Ahlenius et al further disclose that the vectors capable of expressing SOX9, NFIA, and/or NFIB are under control of a tetracycline-controlled transactivator, which is manipulated by the inclusion of exclusion of doxycycline in the culture medium (Paragraphs [0007], [0021]-[0022], [0030], [0047], [0138]-[0148]; Figure 3A). As doxycycline is a tetracycline-based antibiotic, this therefore reads on the method of the instant claim. See Paragraph [0028] of the instant Specification filed 02 March 2023.
Regarding claim 8: Following the discussion of claim 1, Ahlenius et al further disclose that the human pluripotent stem cells are human induced pluripotent stem cells (Paragraphs [0014], [0020], [0024], [0033], [0048]; Table 1; Figure 8). This therefore reads on the method of the instant claim.
Regarding claim 10: Following the discussion of claim 9, Ahlenius et al further disclose that the iAs are co-cultured with induced neurons (Paragraphs [0004]-[0005], [0019], [0049]-[0050]; Figure 1). This therefore reads on the co-culture of the instant claim.
Conclusion
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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633