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 .
Applicants' amendments to the claims and arguments filed on 11-18-2025 have been received and entered. Claims 1, 3, 4, 6, 7, 10, 11, 12, 13, 14 have been amended. Claims 9, 15-20 have been canceled. Claims 21-27 have been added. Claims 1-8, 10-14, and 21-27 are pending.
Election/Restrictions
Applicant's election with traverse of Group 1, claims 1-14, in the reply filed on 02-19-2025 is acknowledged. The traversal is on the ground(s) that the PCT Examiner did not find it a burden to examine all three groups of claims, i.e., claims 1-20, in the Written Opinion issued on April 27, 2021. This is not found persuasive because instant application is a national stage filing under 35 U.S.C. 371 and according to MPEP 1893.03(d), whether or not a serious burden is required is not a proper basis of traversal in a national stage application. According to MPEP 1893.03(d), if national stage application lacks unity of invention, it is required that the applicant elects the invention to which the claims shall be restricted. Moreover, the searching performed by the International Search Authority (ISA) is not relevant to the examiner's finding of the lack of unity for reasons of record. Nevertheless, there is a serious search and examination burden to examine all three groups of claims. The requirement is still deemed proper and is therefore made FINAL.
Claims 15-20 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 02-19-2025. It is noted that claims 15-20 have been canceled in the Applicants' amendments to the claims filed on 11-18-2025.
Claims 1-8, 10-14, and 21-27 are under consideration.
Priority
This application is a 371 of PCT/JP2021/005255 filed on 02/12/2021 that claims priority from foreign applications JP 2020-021843 filed on 02/12/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Withdrawn - Claim Rejections - 35 USC § 112
Claim 1-14 were 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. Applicant's amendments to the claims obviates the basis of the rejection. Applicants' arguments with respect to the withdrawn rejections are thereby rendered moot.
Withdrawn - Claim Rejections - 35 USC § 102
Claims 1-8, 11-12 were rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Hanna et al (Pub .No.: US 2017/0275593 A1, Pub . Date: Sep . 28, 2017). In view of Applicants' amendment of the claims, requiring “suspension culture of pluripotent stem cells” instead of “suspension culture of a pluripotent stem cell” and “wherein the step of performing a suspension culture comprises the step of forming a cell aggregate while maintaining said pluripotent stem cells in said aggregates in the undifferentiated state.”, the previous rejections of claims are hereby withdrawn. Applicants' arguments with respect to the withdrawn rejections are thereby rendered moot. The claims are however subject to new rejections over the prior art of record, as set forth below.
Withdrawn - Claim Rejections - 35 USC § 103
Claims 1, 9-10 were rejected under 35 U.S.C. 103 as being unpatentable over Hanna et al (Pub .No.: US 2017/0275593 A1, Pub . Date: Sep . 28, 2017) in view of Smith et al (Pub. No.: US 2018/0112187 A1, Pub . Date: Apr. 26 , 2018). In view of Applicants' amendment of the claims, the previous rejections of claims are hereby withdrawn. Applicants' arguments with respect to the withdrawn rejections are thereby rendered moot. The claims are however subject to new rejections over the prior art of record, as set forth below.
Claims 1, 13 were rejected under 35 U.S.C. 103 as being unpatentable over Hanna et al (Pub .No.: US 2017/0275593 A1, Pub . Date: Sep . 28, 2017) in view of Gupta et al (Biochemical Engineering Journal 118 (2017) 25–33, DOI: 10.1016/j.bej.2016.11.005, Available online 8 November 2016). In view of Applicants' amendment of the claims, the previous rejections of claims are hereby withdrawn. Applicants' arguments with respect to the withdrawn rejections are thereby rendered moot. The claims are however subject to new rejections over the prior art of record, as set forth below.
Claims 1, 14 were rejected under 35 U.S.C. 103 as being unpatentable over Hanna et al (Pub .No.: US 2017/0275593 A1, Pub . Date: Sep . 28, 2017) in view of Jossen et al (Bioengineering 2018, 5, 106; doi:10.3390/bioengineering5040106, Published: 4 December 2018). In view of Applicants' amendment of the claims, the previous rejections of claims are hereby withdrawn. Applicants' arguments with respect to the withdrawn rejections are thereby rendered moot. The claims are however subject to new rejections over the prior art of record, as set forth below.
New- Claim Objections- necessitated by amendments
Claim 13 objected to because of the following informalities:
Claim 13 has two periods at the end of the claim. It would be remedial to amend the claim to have one period at the end of the claim.
Appropriate correction is required.
New- Claim Rejections - 35 USC § 103- necessitated by amendments
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.
Claims 1-8, 10-12, 21-23, 25-27 are rejected under 35 U.S.C. 103 as being unpatentable over Hanna et al (Pub .No.: US 2017/0275593 A1, Pub . Date: Sep . 28, 2017) in view of Lipsitz et al (Pub .No.: US 2019 /0316081 A1, Pub. Date: Oct. 17 , 2019)
Claim interpretation:
The specification of the claimed invention teaches that specific examples of the PKCβ inhibitor having the above structural formula [Formula I] include a compound selected from the group consisting of Go6983, GF109203X, LY-333531, Enzastaurin, Sotrastaurin, Ro-31-8220-mesylate, Ro-32-0432-hydrochloride, Go6976, Rottlerin, Midostaurin, Daphnetin, Dequalinium Chloride, Baicalein, Quercetin, Luteolin, Bisindolylmaleimide II, Calphostin C, Chelerythrine chloride, L-threo Dihydrosphingosine, and Melittin. Among the PKCβ inhibitors having the above structural formula, a compound selected from the group consisting of Go6983, GF109203X, and LY-333531 is preferably used ([0043], page 22). Thus, Go6983, GF109203X, and LY-333531 are interpreted as PKCβ inhibitors.
The specification of the claimed invention teaches that an example of the TNKS inhibitor can be a compound selected from the group consisting of IWR-1-endo, XAV939, G007-LK G244-LM, MSC2504877, and WIKI4. Among the TNKS inhibitors, IWR-1-endo and/or XAV939 is particularly preferably used ([0061], page 26). Thus, IWR-1-endo and XAV939 are interpreted as TNKS inhibitors.
Regarding to claim 1, Hanna et al teach media for culturing pluripotent stem cells (Title) and provided a method of generating a naive pluripotent stem cell (PSC) ([0033], page 3). Hanna et al teach “The present invention , in some embodiments thereof relates to novel culture media which can be used to generate and expand pluripotent stem cells in general and more particularly naive pluripotent stem cells.” ([0001], page 1). Hanna et al teach the cells may be cultured in a bioreactor such as stirred flask bioreactors, rotating wall bioreactors ([0570]-[0571], page 31), and the use of EBs (Embryoid bodies) that can be used to differentiate EBs into lineage specific cells ([0647], page 34).
Hanna et al also provided a culture medium comprising an AXIN stabilizer and a PKC inhibitor ([0015], page 3). The AXIN complex stabilizer is IWR- 1 ([0315], page 17) and XAV939 ([0318], page 17). Additionally, example of a protein kinase C (PKC) inhibitor is Go6983 ([0324], page 17).
Hanna et al teach single-cell suspensions of primed or naïve PSC ([0266], page 13) and the use of “cell clumps” for culturing the naive PSC ([0581], page 31) and the use of stirred flask bioreactors, rotating wall bioreactors ([0570]-[0571], page 31); however, the base claim 1 has been amended to require “suspension culture of pluripotent stem cells” instead of “suspension culture of a pluripotent stem cell” and further require “wherein the step of performing a suspension culture comprises the step of forming a cell aggregate while maintaining said pluripotent stem cells in said aggregates in the undifferentiated state”. Hanna et al do not specifically mention forming a cell aggregate in suspension culture as amended claim 1 requires. Lipsitz et al cure the deficiency.
Lipsitz et al teach media and methods for expansion of pluripotent stem cells (title), and the method comprises a first step of culturing in a medium comprising inhibitors of PKC (Abstract) such as Go6983 ([0111], page 5). Lipsitz et al teach “a protocol was tested that has been reported to maintain “ naïve” hPSC with enhanced bioprocessing attributes in a cocktail containing 5 inhibitors (5i), including PKC inhibition and p38 inhibition via the BIRB796 molecule” ([0211], page 11). Lipsitz et al teach “One method for scalable expansion of PSC is culture as cell aggregates in dynamic suspension conditions” ([0007], page 1), and “FIG . 2E is images of 5i-HES2 cells and primed HES2 cells. In an orbital shaker suspension bioreactor after 72 hours of culture , 5i-HES2 form a larger number of smaller aggregates than primed HES2” ([0042], page 3). Lipsitz et al teach “In suspension, altered state hPSC had improved single cell survival, more efficient aggregate formation , and enhanced shear tolerance compared to primed hPSC” ([0221], page 14). Thus, a person of ordinary skill in the art would be motivated to form a PSC cell aggregate in suspension to expand an undifferentiated pluripotent stem cell population (For the claimed: wherein the step of performing a suspension culture comprises the step of forming a cell aggregate while maintaining said pluripotent stem cells in said aggregates in the undifferentiated state).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Hanna et al by using orbital shaker suspension bioreactor to form a cell aggregate of undifferentiated
pluripotent stem cell population as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Lipsitz et al teach “Example 4 : culture optimization enables long-term , high-yield maintenance of the pluripotent state in suspension” (Page 12), and “Suspension expansion of two additional lines, WIBR3 hESC and C1.15 hiPSC (FIG . 12C ) in 4i conditions led to significantly enhanced fold expansion (19.0 ± 2.0 and 21.5±2.5-fold expansion respectively ) relative to primed hPSC, demonstrating that this technique is applicable to other hPSC lines including iPSC.” ([0220], page 13-14). Lipsitz et al teach “In suspension, altered state hPSC had improved single cell survival, more efficient aggregate formation , and enhanced shear tolerance compared to primed hPSC” ([0221], page 14). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Lipsitz et al stated that “After 6 days in stirred suspension, untreated PSC displayed large, heterogeneous aggregate morphologies in both bioreactor geometries. Furthermore, in stirred tank bioreactors seeded with DS, PSC were successfully expanded for 3 passages while maintaining high expression of pluripotency markers Oct4 and Sox2 (> 85 % ) (FIG . 17D )” ([0228], page 15).
Regarding to claim 2, 3, 4, Hanna et al teach that according to some embodiments of the invention ,the AXIN stabilizer (e.g., IWR -1, XAV939) is provided at a concentration range of between about 0.1 -70 µM ([0316]-[0318], page 17). Additionally, Go6983 is provided at a concentration range of between about 0.5 - 100 µM, e.g., from about 1 µM to about 100 µM ([0325], page 17). Since the ratio of the concentrations of the PKCβ inhibitor (e.g., Go6983) and the TNKS inhibitor (e.g., XAV939) as taught by Hanna et al can be at least 1:1, the ratio can be in the range of 167:1 and 1:1600.
Regarding to claim 5, Hanna et al teach that the culture medium further comprises at least one agent selected from the group consisting of: a ROCK inhibitor, ascorbic acid etc. ([0016], page 3). Additionally, four-day-old EBs are cultured for 5-12 days in tissue culture dishes including DMEM/F-12 medium with 5 mg/ml insulin , 50 mg/ml transferrin , 30 nM selenium chloride, and 5 mg/ml fibronectin ([0649], page 34).
Regarding to claim 6, Hanna et al teach that the culture medium further comprises at least one agent selected from the group consisting of PI3K activator, a SMAD activator, etc. ([0016], page 3). SMAD activator is TGFβ1 ([0017], page 3). The PI3K activator is FGF2 ([0018], page 3).
Regarding to claim 7-8, Hanna et al teach that the medium further comprises at least one agent selected from the group consisting of: a ROCK inhibitor etc. ([0334], page 18). Non -limiting examples of ROCK inhibitors include Y27632 etc. ([0337], page 18).
Regarding to claim 10, Lipsitz et al teach “Days -2 to 0 are the “re-priming" stage in which 5i-hPSC aggregates are transferred to conventional primed hPSC medium” ([0055], Page 3).
Regarding to claim 11-12, Hanna et al teach a method of improving generation of induced pluripotent stem cells (iPSCs) from a somatic cell, comprising : expressing within the somatic cell a factor selected from the group consisting of Nanog, Oct4 , Sox2, K1f4 , c-Myc etc. ([0622]-[0623], page 33) and “when the somatic cells are subject to de-differentiation using DNA transfection of the growth factors (e.g., at least two of the Oct4, Sox2 , Klf4 and c -Myc ), then the method results in ……..at least about 90 % , e.g., at least about 95 %, at least about 99 % , e.g., 100 % more iPSCs” ([0634], page 33).
Regarding to claim 21, Lipsitz et al teach “methods and reagents for culturing pluripotent stem cells. The method comprises a first step of culturing in a medium comprising inhibitors of GSK -3B , JNK , p38, PKC and Erk1/ 2” (abstract) and “One method for scalable expansion of PSC is culture as cell aggregates in dynamic suspension conditions. The PSC aggregate size distribution and average size is known to affect oxygen and nutrient diffusion throughout the aggregate and the resulting characteristics of the cell product. Lack of control over aggregate size can result in loss of cell viability and pluripotency …... the authors describe herein the use of controlled aggregation of pluripotent stem cells” ([0007], page 1). Thus, it is indicating that controlling aggregate size leading to oxygen and nutrient diffusion was recognized in the prior art to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform the controlling aggregate size, oxygen and nutrient diffusion a plurality of times out of the course of routine optimization, in order to increase cell viability and pluripotency.
Regarding to claim 22, Lipsitz et al teach aggregates have a size range of 30 µm to 1000 µm: FIG . 7 is a histogram depicting aggregate size distribution of primed hPSC and 5i -hPSC. After 3 days in orbital shaker (dynamic ) suspension conditions ([0061], page 3).
PNG
media_image1.png
642
875
media_image1.png
Greyscale
Regarding to claim 23, Hanna et al teach “Cells expanded in the culture medium of some embodiments of the invention (Medium number 138 and 136 retain their pluripotency as is indicated by the high percentage of OCT4 positive cells (93 % and 97 % )” (see [1284], page 59 and example 7 and table 3).
Regarding to claim 25, Hanna et al teach “According to another embodiment, the AXIN complex stabilizer is IWR-1” ([0315], page 17).
Regarding to claim 26-27, Lipsitz et al teach “the pluripotent stem cell aggregates cultured in a medium comprising a polysulfated compound are cultured under dynamic suspension conditions. Dynamic suspension conditions may comprise, for example, culture on an orbital shaker or culture in a stirred tank bioreactor (STR )” ([0153], page 8).
Claims 13 is rejected under 35 U.S.C. 103 as being unpatentable over Hanna et al (Pub .No.: US 2017/0275593 A1, Pub . Date: Sep . 28, 2017) in view of Lipsitz et al (Pub .No.: US 2019 /0316081 A1, Pub. Date: Oct. 17 , 2019) as applied to claims 1-8, 10-12, 21-23, 25-27 above, and further in view of Gupta et al (Biochemical Engineering Journal 118 (2017) 25–33, DOI: 10.1016/j.bej.2016.11.005, Available online 8 November 2016).
The teachings of Hanna et al and Lipsitz et al above are incorporated herein in their entirety. They do not specifically teach measuring lactic acid concentration. Gupta et al cure the deficiency.
Regarding to claims 13, Gupta et al teach the growth of pluripotent stem cells is dependent on various culture conditions. The presence of lactic acid as a metabolic by-product has been reported to be detrimental for mammalian cells in most cases. However, the use of lactate as a source of energy has also been reported for certain cell types. Supplementation with lactate decreased cell proliferation and cell number (Abstract). Fig. 2 shows that cell proliferation for feeder dependent ES and iPSC followed a trend similar to that of the feeder independent ESC. (It is noted that 1 mg/ml of sodium lactate is approximately 8.92 mM). Thus, it is indicating that controlling lactate concentration was recognized in the prior art to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform the controlling lactate concentration a plurality of times out of the course of routine optimization within the range of 5 to 15 mM, in order to increase cell viability.
PNG
media_image2.png
1669
1845
media_image2.png
Greyscale
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of the above references by measuring and optimizing the level of lactic acid in the range of 5 to 15 mM as instantly claimed as taught by Gupta et al, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Gupta et al teach that lactate decreased cell proliferation (abstract), and viable cell count decrease significantly with increasing
sodium lactate concentration (Page 28, left column, 1st para.). Thus, a person of ordinary skill in the art would have been motivated to perform the controlling lactate concentration a plurality of times out of the course of routine optimization to improve cell viability. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Gupta et al were able to measure the level of lactate in ES and iPSC cell cultures and correlate the data with the viability of the cells.
Claims 14 is rejected under 35 U.S.C. 103 as being unpatentable over Hanna et al (Pub .No.: US 2017/0275593 A1, Pub . Date: Sep . 28, 2017) in view of Lipsitz et al (Pub .No.: US 2019 /0316081 A1, Pub. Date: Oct. 17 , 2019) as applied to claims 1-8, 10-12, 21-23, 25-27 above, and further in view of Jossen et al (Bioengineering 2018, 5, 106; doi:10.3390/bioengineering5040106, Published: 4 December 2018).
The teachings of Hanna et al and Lipsitz et al above are incorporated herein in their entirety.
Hanna et al specifically teach the cells may be cultured in a bioreactor (or in multi-level industrial flasks) (see [0570], page 31) and stirred flask bioreactors (see [0571], page 31). Lipsitz et al teach “culture on an orbital shaker or culture in a stirred tank bioreactor (STR )” ([0153], page 8). However, they do not teach stirring culture with a blade tip speed of 0.05 m/s or higher and 1.37 m/s or lower. Jossen et al cure the deficiency.
Regarding to claims 14, Jossen et al teach growth behavior of human adipose tissue-derived stromal/stem cells at small scale (title). Single-use stirred bioreactors in combination with microcarriers (MCs) have shown themselves to be suitable systems for in vitro expansion of human adipose tissue-derived stromal/stem cells (hASCs). Jossen et al comparing the corresponding tip speeds (utip = p n d), similar values for the SP100 and SP300 were calculated (Page 11, last para and Figure 6b and Table 3) (showing tip speeds from 0 – 0.24 m/s on y-axis).
PNG
media_image3.png
659
1432
media_image3.png
Greyscale
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of above references by using stirred bioreactors with tip speeds from 0 – 0.24 m/s for in vitro expansion of stem cells as taught by Jossen et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Jossen et al stated that single-use stirred bioreactors have shown themselves to be suitable systems for in vitro expansion of stem cell (Abstract). Jossen et al also provided particle-related data that allow the bioreactor design to be improved and the optimum growth parameters to yield relevant amounts of therapeutic cells to be determined (Page 26, 2nd para.). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Jossen et al have tested the use of stirred bioreactors with different tip speeds.
Claims 24 is rejected under 35 U.S.C. 103 as being unpatentable over Hanna et al (Pub .No.: US 2017/0275593 A1, Pub . Date: Sep . 28, 2017) in view of Lipsitz et al (Pub .No.: US 2019 /0316081 A1, Pub. Date: Oct. 17 , 2019) as applied to claims 1-8, 10-12, 21-23, 25-27 above, and further in view of Yanagihara et al (WO 2018047941 A1, 2018-03-15).
The teachings of Hanna et al and Lipsitz et al above are incorporated herein in their entirety.
Hanna et al teach A culture medium comprising a PKC inhibitor (Abstract). Lipsitz et al teach the term “ PKC inhibitor” refers to any molecule that inhibits the function of protein kinase C (PKC) such as Go 6983 etc. ([0111], page 5). However, they don’t teach wherein the PKCβ inhibitor is LY-333531. Yanagihara et al cure the deficiency.
Yanagihara et al teach “The present invention pertains to: a medium for culturing stem cells, said medium containing at least one compound selected from the group consisting of a ROCK inhibitor, a PKC inhibitor, a histone methyltransferase inhibitor and a retinoic acid receptor agonist and being free from growth factors or having a low growth factor concentration; a method for culturing stem cells with the use of the medium; a stem cell growth promoter; a cell composition comprising stem cells or cells differentiated therefrom; and a method for producing the cell composition” (Abstract). Stem cells include pluripotent stem cells (Page 4). Examples of the PKC inhibitor include LY333531 (Page 8).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of above references by using PKC inhibitor include LY333531 as taught by Yanagihara et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Yanagihara et al teach that “the present invention relates to a medium for culturing stem cells, which comprises adding a compound capable of efficiently culturing stem cells to a medium not containing a growth factor or having a low concentration of growth factor” (Page 2) and “The method of the present invention is characterized by efficiently proliferating stem cells having differentiation potential while maintaining the undifferentiated state of the stem cells by culturing the stem cells in the medium of the present invention” (Page 10). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Yanagihara et al were successful in expanding undifferentiated stem cells with detailed instructions and data.
Response to Arguments
Applicant's arguments filed 11-18-2025 have been fully considered but they are not persuasive.
Applicant argue that “the cell aggregates are formed in suspension culture while the cells are still in the undifferentiated state because a PKBB inhibitor and a TNKS inhibitor are both used in the culture while the cells are still in the undifferentiated state. This is an unexpected result that is not suggested or made obvious in the prior art. Claim I has been amended to clarify features related to this unexpected result” (remarks, page 7).
Response to Arguments:
Applicants argue an “unexpected result”; however, using cited inhibitor agents in culturing pluripotent stem cell culture or maintaining undifferentiated state in suspension is not unexpected result in view of Hanna et al and Lipsitz et al (see rejection above). Hanna et al teach media for culturing pluripotent stem cells (Title) and provided a method of generating a naive pluripotent stem cell (PSC) ([0033], page 3). Hanna et al also provided a culture medium comprising tankyrase (TNKS) inhibitor IWR- 1 ([0315], page 17) and XAV939 ([0318], page 17) and protein kinase C (PKC) inhibitor Go6983 ([0324], page 17). Lipsitz et al teach media and methods for expansion of pluripotent stem cells (title), and the method comprises a first step of culturing in a medium comprising inhibitors of PKC (Abstract) such as Go6983 ([0111], page 5). Lipsitz et al teach “a protocol was tested that has been reported to maintain “naïve” hPSC with enhanced bioprocessing attributes in a cocktail containing 5 inhibitors (5i), including PKC inhibition and p38 inhibition via the BIRB796 molecule” ([0211], page 11). Lipsitz et al teach “In suspension, altered state hPSC had improved single cell survival, more efficient aggregate formation , and enhanced shear tolerance compared to primed hPSC” ([0221], page 14). Thus, a person of ordinary skill in the art would be motivated to form a PSC cell aggregate in suspension to expand an undifferentiated pluripotent stem cell population. One of ordinary skill in the art would have been motivated to combine teachings of Hanna et al with the teachings of Lipsitz et al because Lipsitz et al teach “Example 4 : culture optimization enables long-term , high-yield maintenance of the pluripotent state in suspension” (Page 12), and “Suspension expansion of two additional lines, WIBR3 hESC and C1.15 hiPSC (FIG . 12C ) in 4i conditions led to significantly enhanced fold expansion (19.0 ± 2.0 and 21.5±2.5-fold expansion respectively ) relative to primed hPSC, demonstrating that this technique is applicable to other hPSC lines including iPSC.” ([0220], page 13-14). Lipsitz et al teach “In suspension, altered state hPSC had improved single cell survival, more efficient aggregate formation , and enhanced shear tolerance compared to primed hPSC” ([0221], page 14).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHOA NHAT TRAN whose telephone number is (571)270-0201. The examiner can normally be reached M-F (9-5).
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, PETER PARAS can be reached at (571)272-4517. 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.
/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
Prosecution Insights