DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, 18269270, US 20240060051, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-2, 4-6, 10-22 and 41-42 are pending.
Priority
The filing receipt, mailed 11/17/2023, states that this application is a 371 of PCT/JP2021/048397, 12/24/2021, and claims Foreign Priority benefit of JAPAN 2020-217472, filed 12/25/2020.
It is noted that a certified English language translation, filed 2/6/2026, of the foreign priority document, JAPAN 2020-217472, filed 12/25/2020, is now of record. Therefore, foreign priority benefit to JAPAN 2020-217472, filed 12/25/2020, has been perfected.
Response to Amendment
1. The rejection of Claim 19 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn as overcome by applicant’s amendment, filed 2/2/2026.
2. The rejection of Claim(s) 1, 2, 5, 6, 14, 15, 21, 22 is/are rejected under 35 U.S.C. 102(a)(1) and (2) as being anticipated by Grewal, US 11,981,932, filed 6/16/2021, is withdrawn as overcome by applicant’s amendment, filed 2/2/2026.
Claim Interpretation
Claim 1 has been amended to include the language “ wherein the one or more vectors are temperature-sensitive in the cell culture environment for establishing native pluripotent stem cells.” This compares to the language of now canceled claim 9, which stated: “The method according to claim 7, wherein the one or more vectors that are temperature-sensitive in the cell culture environment for establishing naïve pluripotent stem cells,” (claims, filed 6/22/2023). Now canceled claim 7 was in turn dependent on original claim 1, (currently amended):
7. (currently amended): The method according to claim 1, wherein the one or more vectors are selected from the group consisting of a temperature-sensitive vector, a vector containing a target sequence of a microRNA specific for induced pluripotent stem cells, and a temperature-sensitive vector containing a target sequence of a microRNA specific for induced pluripotent stem cells.
1. (original): A method for producing naive induced pluripotent stem cells from human somatic cells, comprising the following steps (1) to (3): (1) introducing one or more vectors containing a reprogramming factor into human somatic cells, (2) culturing said somatic cells in the presence of a naive medium, and (3) after step (2), culturing the resulting cells in the presence of the naive medium under the condition in which the amount of the vectors per the somatic cell is reduced to 30% or less of that at the start of step 3.
Instant claims.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
1. Claim(s) 1-2, 4-6, and 10-22 and 41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Grewal, US 11,981,932, filed 6/16/2021, claiming domestic priority to US provisional-applications US 63040392, filed 20200617; US 63040397, filed 20200617; US 63040398, filed 20200617; US 63040373, filed 20200617; US 63040374, filed 20200617; and of Pre-Grant Publication, US 2021/0395697, published 12/23/2021 as applied to claims 7, 9-13, and 16-20, above, and further in view of Nakanishi, US 20100311171; Ban, US 20160215270; Saeki, US 20200283797; and Takebe, US 20220213444.
Grewal, US 11,981,932, teaches throughout the publication and abstract, and e.g., Col. 1, line 36, teaches that gene expression profiles in somatic cells can be changed to epigenetically reprogram them into pluripotent stem cells. At col. 1, lines 65, transcription factors Oct3/4, Sox2, Klf4 and c-Myc may confer pluripotency upon adult somatic cells and for generating iPSCs, (Induced Pluripotent Stem Cell).
Grewal, at col. 2, lines 6-19, states:
Against this backdrop, there is still a need for improved materials and methods for reprograming somatic cells into pluripotent state(s). In one aspect, provided herein are methods of producing induced pluripotent stem cells (iPSCs) comprising: (a) contacting an isolated population of cells with an activation culture; wherein the activation culture comprises IL-15 and zoledronic acid; (b) culturing the isolated population of cells in the activation culture to enrich and/or activate γδ T cells in the isolated population of cells; (c) transducing the γδ T cells with a viral vector encoding one or more reprogramming factors; and (d) culturing the transduced γδ T cells under conditions suitable for reprogramming mammalian somatic cells to a pluripotent state.
Grewal, at col. 2, lines 6-19.
Grewal at claim 1 claims a method of producing human induced pluripotent stem cells. Grewal, at col. 2, line 22-23, teaches the viral vector is a Sendai virus vector. Grewal, at col. 25, lines 25-61, describes Sendai virus vectors encoding one or more reprograming factor OCT3/4, SOX2, KLF4, LIN28, and c-Myc;. Grewal, at col. 56, line 21-col. 57, line 42, describes that after Sendai Virus infection of peripheral blood mononuclear cells (see, Grewal at col. 13, TABLE 1, for definition of “PBMC”) or γδ T cells, (Day 0), the cells were cultured (Day 1) the viruses were removed, (which reasonably reads on 0% virus concentration, which is less than 30%, as claimed), followed by cell transfer and culture (Day 1), as in claims 18, 22, and in the absence of feeder cells as in claim 21. On Day 3, the transduced cells were transferred to feeder layer cultures.
Grewal does not teach temperature sensitive Sendai virus vectors, microRNA, TS mutations, temperatures above 80 degrees centigrade, and specific naïve media or media with specific inhibitors or stimulators.
Nakanishi, US 20100311171, throughout the publication and abstract, teaches at e.g., that stem cell reprogramming genes, such as Oct3/4, Sox2, Klf4 and c-Myc, as in claims 14, 15, 16, 17, (see e.g., para [0026]), cloned into a single sustained expression-type Sendai viral vector are shown to reprogram differentiated somatic cells into induced pluripotent stem (iPS) cells without integration of vector sequences into the host cell's genome. The genes are transduced into normal differentiated somatic cells via infection with recombinant Sendai virus. Sendai virus remain episomal inside infected cell, see, e.g., para [0122]. After expression of the reprogramming genes and subsequent induction of pluripotency, the vector genome RNA including the reprogramming genes is removed from the cell to establish an iPS cell that is genetically identical to the parent somatic differentiated cell thus reducing the risk of tumorigenic transformation caused by random integration of vector sequences into the host genome. The method promises to provide safe, autologous iPS cells that can be used for human cell replacement and regeneration therapeutic applications. Nakanishi at p. 10, para [0129], teach artificial insertion of target sequences for specific miRNA can be used to remove the loaded Sendai viral vector. At para [0129], the reprogramming gene-loaded Sendai viral vector can be removed in the same manner as that used in the siRNA approach by adding a target sequence for miRNA to an L, NP or P gene-noncoding region of the Sendai viral vector. Expression of miRNA in the cell then suppresses expression of the L, NP or P gene, as in claim 12.
Ban, US 20160215270, throughout the publication and abstract, and e.g., [0251], teaches temperatures for removing temperature sensitive vectors: [0251] From the colonies of cells which have completed reprogramming, cells from which the vectors have been removed can be selected appropriately. For example, cells from which the vectors have been naturally removed may be selected. To this end, for example, negative selection can be carried out using antibodies specific to the virus vectors (for example, anti-HN antibodies). Furthermore, when using temperature-sensitive vectors, the vectors can be removed easily by culturing at normal temperatures (for example, about 37° C., specifically 36.5° C. to 37.5° C., preferably 36.6° C. to 37.4° C., and more preferably 36.7° C. to 37.3° C.), or by culturing at slightly high temperatures (for example, 37.5° C. to 39° C., preferably 38° C. to 39° C., or 38.5° C. to 39° C.), as in claim 11 When SeV(PM)/TSΔF, or vectors with further introduction of mutations such as TS 7, TS 12, TS 13, TS 14, or TS 15 into SeV(PM)/TSΔF are used, passaging leads to natural loss of the vector. Examples of preferred vectors include the combination of SeV(PM)KOS/TS12ΔF and SeV18+KLF4/TSΔF, but are not limited thereto. Furthermore, in this case, the MYC gene can be introduced using SeV(HNL)c-rMYC/TS1.2ΔF, SeV(HNL)c-rMYC/TS13ΔF, SeV(HNL)c-rMYC/TS15ΔF, or such. The combination of SeV(PM)KOS/TS12ΔF, SeV18+KLF4/TSΔF, and SeV(HNL)c-rMYC/TS15ΔF is particularly preferable. Furthermore, not loading the MYC gene into the Sendai virus vectors carrying the KLF gene, OCT gene, and SOX gene has the advantage that reprogramming can be done without use of the carcinogenesis-related MYC gene. This is also advantageous because it is possible to freely select the fourth factor for use from c-MYC, L-MYC, Glis1, or such in addition to the KLF gene, OCT gene, and SOX gene.
Saeki, US 20200283797, teaches throughout the publication and abstract, and e.g., claim 5, and at para [0124], For example, mutations in Sendai virus, such as TS 7 (Y942H/L1361C/L1558I mutations in the L protein, as in claim 10), TS 12 (D433A/R434A/K437A mutations in the P protein), TS 13 (D433A/R434A/K437A mutations in the P protein and L1558I mutation in the L protein), TS 14 (D433A/R434A/K437A mutations in the P protein and L1361C in the L protein), TS 15 (D433A/R434A/K437A mutations in the P protein and L1361C/L1558I mutations in the L protein), as described in detail in WO 2012/029770 and WO 2010/008054 are preferable temperature-sensitive mutations.
[0125] A specific example of the vector may be an F gene-deleted type Sendai virus vector (for example, Z strain) having G69E, T116A, and A183S mutations in the M protein; A262T, G264R, and K461G mutations in the HN protein; L511F mutation in the P protein; and N1197S and K1795E mutations in the L protein, and a vector obtained by further introducing a mutation of TS 7, TS 12, TS 13, TS 14, or TS 15 into the aforementioned vector is more preferred. Specifically, examples include SeV18+/TSΔF (WO 2010/008054 and WO 2003/025570), SeV(PM)/TSΔF, and vectors that have been modified so as to have microRNA target sequences added to the NP gene, P gene, or L gene in the vectors obtained by further introducing a mutation of TS 7, TS 12, TS 13, TS 14, or TS 15 into the aforementioned vectors.
Saeki, e.g., at para [0298], , teaches TS12 and TS 15, as in claim 10; at Examples 1-4 and e.g., para [0300], [0308], claim 8, teaches mir-367, as in claims 12, 13;
Takebe, US 20220213444, throughout the patent and abstract, and at e.g., para [0121], teaches compositions and methods for reprogramming induced pluripotent stem cells, such as from a primed to naïve state. Takebe, at p. 1, para [0005], teach T2iLGö , tt2iLGö medium; at para [0006], teaches culture medium for producing naïve pluripotent stem cells comprising a GSK3 inhibitor, Leukemia inhibitory factor (LIF), PKC inhibitor, and a cAMP activator, as in claim 19. Takebe remains prior art, at least, because the filing date of the PCT/US2020/035387 371 priority document is 5/29/2020. Takebe at para [162] teaches a medium containing PD 0325901, a MEK inhibitor, as in claim 41.
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined the various temperature sensitive Sendai virus vectors, microRNA, TS mutations, temperatures above 80 degrees centigrade, and specific naïve media or media with specific inhibitors or stimulators, as taught by the prior art with the methods for reprogramming somatic cells into pluripotent stem cells, as taught by Grewal.
One of ordinary skill in the art would have motivated to have combined temperature sensitive Sendai virus vectors, microRNA, TS mutations, temperatures above 80 degrees centigrade with the known methods for reprogramming somatic cells into pluripotent stem cells because the uses of temperature sensitive mutant Sendai vector systems have been shown to facilitate and improve the elimination of the Sendai episomal vectors from the infected stem cells. One of ordinary skill in the art would have employed the various claimed media, with the claimed additives, because these media and modification were shown to support stem cell growth.
2. Claim(s) 41-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Grewal, US 11,981,932, Nakanishi, US 20100311171; Ban, US 20160215270; Saeki, US 20200283797; and Takebe, US 20220213444, as applied to claims 1-2, 4-6, and 10-22 and 41 above, and further in view of Lister, US 20220403343.
The teachings of Grewal, US 11,981,932, Nakanishi, US 20100311171; Ban, US 20160215270; Saeki, US 20200283797; and Takebe, US 20220213444 are relied upon as above.
Grewal, US 11,981,932, Nakanishi, US 20100311171; Ban, US 20160215270; Saeki, US 20200283797; and Takebe, US 20220213444 does not teach temperature sensitive Sendai virus vectors, microRNA, TS mutations, temperatures above 80 degrees centigrade, and specific naïve media or media with specific inhibitors or stimulators.
Grewal, US 11,981,932, Nakanishi, US 20100311171; Ban, US 20160215270; Saeki, US 20200283797; and Takebe, US 20220213444 do not teach or suggest culture medium comprising a MEK inhibitor, and 5iLAF.
Lister, US 20220403343, producing an induced pluripotent stem cell (iPSC). Lister, at para 34, 185, 186, culture medium comprising a MEK inhibitor, as in instant claim 41. Lister, at para [0034]-[0040], teaches media containing a KEK inhibitor and definitions of “naïve pluripotent state.” Lister, at Table 2, and reference claim 11, teach 5iLAF, as in instant claim 42.
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined MEK inhibitors, and 5iLAF, as taught by Lister, in media used to produce pluripotent, naïve human stem cells.
One of ordinary skill in the art would have motivated to have combined MEK inhibitors, and 5iLAF, because these media and modification were shown to support pluripotent naïve stem cell growth. The state of art of inducing and maintaining pluripotent naïve human stem cells at the time of filing, as taught by the prior art references of Grewal, US 11,981,932, Nakanishi, US 20100311171; Ban, US 20160215270; Saeki, US 20200283797; and Takebe, US 20220213444, included the cell culture media use of various factors, including MEK inhibitors, and 5iLAF. Furthermore, the use of temperature sensitive viral vectors for gene expression, has long been known in the art.
Conclusion
1. All pending claims, Claims 1-2, 4-6, and 10-22 and 41-42, are rejected.
2. 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.
3. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark L Shibuya whose telephone number is (571)272-0806. The examiner can normally be reached M-F, 9AM-4:30PM.
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MARK L. SHIBUYA
Primary Patent Examiner
Art Unit 1631
/MARK L SHIBUYA/Primary Patent Examiner, Art Unit 1631
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