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 .
Claim Status
As of the Non-Final Office Action mailed 8/22/2025, claims 1-5 were pending.
In Applicant's Response filed on 11/24/2025, claims 1 and 3-5 were amended, claim 2 was canceled, and claims 6-7 were newly added.
As such, claims 1 and 3-7 are pending and have been examined herein.
Withdrawn Objections/Rejections
The objection of record to the drawings for minor informalities has been withdrawn.
The objection of record to claim 1 for minor informalities has been withdrawn in view of Applicant’s amendments.
The rejection of record of claims 1-5 under 35 USC § 112(a) have been withdrawn in view of Applicant’s amendments.
The rejection of record of claims 1-2 under 35 USC § 102(a)(1) and (a)(2) as being anticipated by Pawlowski et al (WO2020239807A1, 5/27/2020; Published 12/3/2020; Ref. B1 of Foreign Patent Documents in IDS filed 11/8/2023) has been withdrawn in view of Applicant’s amendments.
The rejection of record of claims 1-5 under 35 USC § 102(a)(1) and (a)(2) as being anticipated by Chen et al (Stem Cells Report, 8 April 2021; 16(5):1363-1380. Ref. B2 of Non-Patent Literature in IDS filed 11/8/2023) has been withdrawn in view of Applicant’s amendments.
New Grounds of Rejections Necessitated by Amendments
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.
Claim(s) 1 and 3-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (Stem Cells Report, 8 April 2021; 16(5):1363-1380. Ref. B2 of Non-Patent Literature in IDS filed 11/8/2023; previously cited) in view of Pawlowski et al (WO2020239807A1, 5/27/2020; Published 12/3/2020; Ref. B1 of Foreign Patent Documents in IDS filed 11/8/2023; previously cited).
Chen teaches the efficient conversion of human induced pluripotent stem cells into microglia by forced expression of both SPI1 and CEBPA (Summary). The reference teaches that during development, various transcription factors (TFs), including RUNX1 (Runt-related transcription factor 1), SPI1 (SFFV pro-viral integration 1), IRF8 (interferon regulatory factor 8), TAL1 (stem cell leukemia/T cell acute lymphoblastic leukemia 1), and SALL1 (Sal-like protein 1), orchestrate the commitment of yolk sac myeloid precursors into brain microglia (Introduction, para 2). By screening seven of the TFs involved in defining microglial cell fate during embryogenesis, we found that overexpression of two genes, SPI1 and CEBPA, in hiPSCs led to the generation of IBA1-positive microglia-like cells within 10 days (Introduction para 4) (“A method for microglia, comprising: introducing, into pluripotent stem cells, a nucleic acid including an open reading frame of a transcription factor that increases expression of a Complement C3 (C3) gene, wherein the transcription factor is a combination of two or more transcription factors selected from the group consisting of CEBPA” as in instant claim 1 in-part; “wherein the transcription factor includes at least CEBPA” as in instant claim 3; “wherein the transcription factor is two or more transcription factors including at least CEBPA” as in instant claim 4; “wherein the transcription factor is three or more transcription factors including at least CEBPA” as in instant claim 5; “a method of producing microglia, comprising: introducing, into pluripotent stem cells, a nucleic acid including an open reading frame of a transcription factor that increases expression of a Complement C3 (C3) gene, wherein the transcription factor comprises a combination of two or more transcription factors selected from the group consisting of CEBPA, . . . , and the transcription factor further comprises one or more transcription factors selected from the group consisting of SPIl, . . . , RUNX1” as in instant claim 6 in-part; “method of producing microglia, comprising: introducing, into pluripotent stem cells, a nucleic acid including an open reading frame of a transcription factor that increases expression of a Complement C3 (C3) gene, wherein the transcription factor is a combination of two or more transcription factors selected from the group consisting of CEBPA, . . . , and at least one transcription factor selected from the group consisting of. . . , RUNX1” as in instant claim 7 in-part). The transcriptome profile of these hiPSC-derived microglia-like cells (induced microglia, or iMGs) resembles human primary microglia, and they show similar physiological functioning, including lipopolysaccharide/interferon-γ (LPS/IFN-γ)-induced inflammatory responses, phagocytic ability, and ADP/ATP-evoked signaling/migration (same para).
Chen does not explicitly teach that the transcription factors increase the expression of C3 gene, however, Applicant’s instant disclosure evidences that at least SPI1 and CEBPA have the requisite structure for the instantly claimed function of “increasing expression of C3 gene.” Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) (see MPEP 2112.01(I)). "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP 2112.01(II)).
The difference between Chen and the instantly claimed invention is that it does not teach the additional use of CEBPB, KLF6, NFIC or PAX8 to produce microglia (as in instant claims 1 in-part, 6 in-part, and 7 in-part).
Pawlowski teaches a method for the production of microglia from human pluripotent stem cells comprising a) targeted insertion of a nucleotide sequence encoding a transcriptional regulator protein into a first genomic safe harbor site; and b) targeted insertion of the coding sequence of the transcription factor PU.1 (i.e., SPI1) into a second genomic safe harbor site, wherein the gene is operably linked to an inducible promoter, which is regulated by the transcriptional regulator protein expression of PU.1; and
c) culturing the stem cells received from steps a) and b) with exposure to at least one growth factor or small molecule that recapitulates signaling during at least one stage of embryonic development of microglia or adult microglia proliferation, differentiation or polarization (see claim 1 of Pawlowski). The method further comprises insertion of the coding sequence of the gene of the transcription factor CEBPB and RUNX1 and expression thereof (see claims 6 and 7 of Pawlowski) (“CEBPB” as in instant claim 1 in-part, instant claim 6 in-part, and instant claim 7 in-part). This shows that CEBPB can be combined with at least SPI1 and RUNX1 to produce microglia from pluripotent stem cells.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to produce microglia from pluripotent stem cells using at least CEBPA as taught by Chen, where CEBPB is also used as taught by Pawlowski, to arrive at the instantly claimed invention. Chen shows that CEBPA, SPI1, and RUNX1 are needed to form microglia. Pawlowski shows that at least CEBPB, SPI1, and RUNX1 can be used to form microglia. One of ordinary skill would have been motivated to combine at least the CEBPA transcription factor of Chen with the CEBPB transcription factor of Pawlowski according to known methods to yield the predictable result of producing microglia as taught by the prior art.
Response to Arguments
Applicant’s arguments regarding the 102 rejections of the previous non-final Office action have been fully considered but are not persuasive. The combination of Chen (previously cited) and Pawlowski (previously cited) render prima facie obvious the transcription factors instantly claimed in the amended method claims of 1 and 3-7 as above.
Conclusion
No claim is allowed.
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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/G.R./Examiner, Art Unit 1632
/KARA D JOHNSON/Primary Examiner, Art Unit 1632