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 .
The response filed 07/17/2026 has been received and entered. Claims 1-5, 7-23, 27, and 29-31 remain pending and have been considered on the merits.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 1-11, 14-15, 17, 20, 22-23, 27, and 29 under 35 U.S.C 103 over Yamanaka et al in view of Gibco
Applicants traverse the rejection of record on the grounds that a seeding density 0.25x104 cells/cm2 TRA-1-60 positive cells produces the unexpected results of decreasing the amount of viral vector in the cells. Applicants point to Example 3 and Fig. 4 of the specification which teaches infecting mononuclear cells with RNA viral vector harboring a reprogramming factor; seeding cells at a concentration greater than 0.25x104 cells/cm2 for the first through fifth passage; then seeding cells at a concentration of 0.25x104 cells/cm2 or less from the sixth passage onward. The reprogramming factor rapidly decreased from the sixth passage onward. Applicants argue these results are unexpected because Yamanaka and Gibco do not teach or suggest controlling a concentration of seeded cells to decrease a virus concentration in the cells. Additionally, applicants have amended claim 1 to require the proportion of cells in which the RNA viral vector remains among the TRA-1-60 positive cells is 4% or less after passage culturing.
In response, the argument has been fully considered but is not found persuasive. Gibco teaches a method of generating vector-Free iPSCs including optimizable steps (See rejection of claim 1 below).
Furthermore, while applicants argue plating the specific amount of 0.25x104 cells/cm2 or less led to the decrease in viral vector positive cells, this result was only achieved after the sixth round of passaging. Therefore, it cannot be determined that the results were achieved as a result of plating density, as a result of the number of passages, or from a combined effect requiring low plating density and six or more rounds of passaging. The claims do not require the cells to be passaged more than once, thus the method as claimed would not necessarily produce TRA-1-60 positive cells with fewer viral vector positive cells.
The rejection over claims 1-5, 7-11, 14-15, 17, 20, 22-23, 27, and 29 has been modified and maintained in response to the claim amendments.
Claim 6 has been cancelled rendering its rejection moot.
RE: Rejection of claims 1-17, 20, 22-23, 27, and 29 under 35 U.S.C. 103 over Yamanaka et al in view of Gibco and Willmann et al
Applicants argue Willman et al does not teach culturing TRA-1-60 positive cells at 0.25x104 cells/cm2 or less and is only relied upon for its teaching that reprogrammed cells outgrow non-pluripotent cells and partially reprogrammed cells without the need for clonal selection.
Given that the modified rejection of claim 1 requires steps of passaging clones in order to remove the viral vector from the TRA-1-60 positive cells of Yamanaka et al, the rejection over claims 1-5, 7-17, 20, 22-23, 27, and 29 is withdrawn.
Claim 6 has been cancelled rendering its rejection moot.
RE: Rejection of claims 1-11, 14-15, 17-20, 22-23, 27, and 29 under 35 U.S.C. 103 over Yamanaka et al in view of Gibco and Sarafian et al.
Applicants argue Sarafian et al does not teach culturing TRA-1-60 positive cells at 0.25x104 cells/cm2 or less or controlling the concentration of seeded cells to decrease the concentration of viral vector remaining in the cells.
In response, it would have been obvious to optimize the seeding density of TRA-1-60 positive cells based on the teachings of Yamanaka et al and Gibco et al (See rejection of claim 1 below).
The rejection over claims 1-5, 7-11, 14-15, 17-20, 22-23, 27, and 29 is maintained.
Claim 6 has been cancelled rendering its rejection moot.
RE: Rejection of claims 1-11, 14-15, 17, 20-23, 27, and 29 under 35 U.S.C. 103 over Yamanaka et al in view of Gibco and Tanabe et al
Applicants argue Tanabe et al does not teach culturing TRA-1-60 positive cells at 0.25x104 cells/cm2 or less or controlling the concentration of seeded cells to decrease the concentration of viral vector remaining in the cells.
In response, it would have been obvious to optimize the seeding density of TRA-1-60 positive cells based on the teachings of Yamanaka et al and Gibco et al (See rejection of claim 1 below).
The rejection over claims 1-5, 7-11, 14-15, 17, 20-23, 27, and 29 is maintained.
Claim 6 has been cancelled rendering its rejection moot.
RE: Rejection of claims 1-11, 14-15, 17, 20, 22-23, and 27-29 under 35 U.S.C. 103 over Yamanaka et al in view of Gibco and Abcam
Applicants argue Abcam et al does not teach culturing TRA-1-60 positive cells at 0.25x104 cells/cm2 or less or controlling the concentration of seeded cells to decrease the concentration of viral vector remaining in the cells and was only relied upon for its teaching of when cells should be split (i.e. the limitations of claim 28).
Given that claim 28 has been cancelled, the rejection over claims 1-5, 7-11, 14-15, 17, 20, 22-23, 27, and 29 is withdrawn.
Claims 6 and 28 have been cancelled rendering its rejection moot.
Claim Objections
Claims 12, 13, and 16 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Maintained/New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 5 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 5 requires the reprogramming factor is RNA. Claim 1 has been amended to require an RNA viral vector carrying a reprogramming factor. Given that the viral vector of claim 1 is an RNA viral vector, the reprogramming factor of the RNA viral vector of claim 1 would necessarily be an RNA. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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.
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 1-11, 14-15, 17, 20, 22-23, 27, 29, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Yamanaka et al (US20160122720A1) in view of Gibco (Reprogramming Fibroblasts with CytoTune, 2012).
Yamanaka et al teaches a method of producing iPS cells from human dermal fibroblasts comprising steps of (i) introducing reprogramming factors into somatic cells; (ii) culturing the cells obtained in step (i) for more than 11 days and not more than 29 days; (iii) sorting TRA-1-60 positive cells from the cells obtained in step (ii); (iv) culturing the TRA-1-60 positive cells sorted in step (iii); (v) transferring a colony obtained in step (iv) to another culture vessel; and (vi) culturing the cells obtained in step (v) thereby obtaining iPS cells (See abstract and ¶0019). Yamanaka et al discloses performing steps (i) and (iv) at 37° C (See ¶0079). The transduction step of Yamanaka et all comprises mixing viruses comprising reprogramming factors and exposing the viruses to HDF cells in a culture medium comprising 10% FBS (See ¶0094). Post transduction, the cells are replated onto feeder cells (See ¶0094). In step (v), single colonies can be separately picked up and subcultured in a separate vessel or a plurality of colonies can be picked up and transferred together in another culture vessel and cultured in bulk (See ¶0088). Additionally, the cells obtained in step (v) are preferably subcultured 10 times or more. Step (iv) can be performed by culturing the TRA-1-60 positive cells in a bFGF-containing culture medium for primate ES cell (See ¶0083). The reprogramming factor can be in the form of a protein, DNA, or RNA and can be introduced into a somatic cell using a viral vector, plasmid, artificial chromosome, lipofection, or liposome microinjection (See ¶0070-0072). The reprogramming factors comprise Oct3/4, Sox2, and Klf4 (See claim 2). In embodiments where a viral vector is used the viral vector can include a retrovirus, lentivirus, adenovirus, adeno associated virus, or a Sendai virus (See ¶0071).
Regarding claims 1-4: Yamanaka et al discloses a method of producing iPS cells, which can include introducing RNA reprogramming factors using a viral vector, comprising the following steps:
introducing reprogramming factors into somatic cells;
culturing the cells obtained in step (i) for more than 11 days and not more than 29 days;
sorting TRA-1-60 positive cells from the cells obtained in step (ii);
culturing the TRA-1-60 positive cells sorted in step (iii);
transferring a colony obtained in step (iv) to another culture vessel; and
culturing the cells obtained in step (v) thereby obtaining iPS cells.
Yamanaka et al therefore discloses a method for manufacturing pluripotent stem cells comprising step (i) which reads on a step of infecting cells with an RNA viral vector carrying a reprogramming factor, thereby introducing reprogramming factors into cells. Step (iii) of Yamanaka et al teaches sorting TRA-160 positive cells obtained in step (ii) thus, step (ii) reads on culturing the cells into which the reprogramming factor is introduced, until the cells become TRA-1-60 positive. Steps (iii) through (v) of Yamanaka et al read on passage culturing the TRA-1-60 positive cells by seeding the TRA-1-60 positive cells. Yamanaka et al further discloses the cells obtained in step (v) are preferably subcultured 10 times or more which further reads on passage culturing the seeded TRA-1-60 positive cells.
Yamanaka et al does not teach seeding the TRA-1-60 positive cells at a concentration of 0.25x104 cells/cm2 or less ,1.25x103 cells/cm2 or less, a density where 11 or more of the seeded cells do not come in contact with each other, or 5% or less confluency.
Gibco teaches a method of producing iPSCs. In a troubleshooting guide, Gibco teaches if there are too many colonies on the plate, the number of cells plated after transduction should be decreased (See Sec. Troubleshooting).
Given that Yamanaka et al teaches a method of producing iPSCs comprising a step of transducing cells with reprogramming factors (i.e. step (i)) and Gibco teaches the number of cells plated after transduction should be decreased if too many colonies form on the plate, it would have been prima facie obvious, before the effective filing date, to optimize the seeding density of the TRA-1-60 positive cells of Yamanaka et al, and arrive at the claimed seeding densities, in order to optimize the number of colonies produced. Where the general conditions of a claim are disclosed in the prior art it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP2144.05(II).
Additionally, Yamanaka et al does not disclose that after passage culturing, the RNA viral vector is only present in 4% or less of the TRA-1-60 positive cells.
Gibco teaches a method of generating vector-Free iPSCs using Sendai reprogramming vectors (See pg. 9, Sec: Generating Vector-Free iPSCs). Gibco teaches the time needed to derive vector-free iPSCs may vary depending on culture and passage conditions (See pg. 9, Sec. Guidelines for generating vector-free iPSCs). Gibco teaches subcolony cloning can be performed for five passages, then testing can be performed to check for virus free iPSCs (See pg. 9, Sec. Guidelines for generating vector-free iPSCs). Furthermore, Gibco teaches if virus positive iPSCs are found, the subcloning can be repeated until no virus positive iPSCs are found (reads on 4% or less). Thus Gibco teaches producing colonies without viral vectors is an optimizable step.
Given that both Yamanaka et al and Gibco teach methods of producing iPSCs comprising steps of introducing RNA reprogramming factors with a viral vector into somatic cells, culturing the cells until they become TRA-1-60 positive, then picking colonies for clonal expansion and Gibco further teaches subcolony cloning can be repeated until vector-free iPSCs are produced, it would have been prima facie obvious to optimize the number of subcloning steps, in the iPSC production method of Yamanaka et al in order to produce vector-free iPSCs (i.e. no iPSCs are positive for the viral vector). Where the general conditions of a claim are disclosed in the prior art it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP2144.05(II)
Regarding claim 5: Following the discussion of claim 1 above, Yamanaka et al discloses the reprogramming factor can be RNA.
Regarding claims 7 and 8: Following the discussion of claim 1 above, Yamanaka et al discloses the reprogramming factor can be introduced into cells using a viral vector such as a Sendai virus.
Yamanaka et al does not disclose using a viral vector that is temperature-sensitive in which stability of a viral nucleic acid decreases at a certain temperature or higher.
Gibco discloses instructions for reprogramming fibroblasts using the CytoTune iPS reprogramming kit. The CytoTune kit comprises Sendai virus (SeV) based vectors capable of expressing Oct4, Sox2, Klf3, and c-Myc (See Sec. Introduction, last paragraph). The CytoTune SeV vectors comprise a c-Myc expressing vector with a functional temperature sensitivity mutations that allow the host cell to be cleared of vectors and reprogramming factor genes by incubating cells at 38-39°C for 5 days (See Sec. Introduction, 3rd paragraph, and pg. 10, Step 4. Note).
Given that Yamanaka et al discloses a method of producing iPSCs using a SeV and Gibco discloses a SeV comprising c-Myc which has a temperature sensitive mutation that allows the host cells to be cleared of the SeV and c-Myc by culturing the cells at 38-39°C (reads on certain temperature) for 5 days, it would have been prima facie obvious to modify the method of Yamanaka et al to use the temperature sensitive SeV of Gibco. One would have been motivated to use the SeV of Gibco in the method of Yamanaka et al because the SeV of Gibco comprises a mutation that allows the host cell to be cleared of vectors and reprogramming factors by incubating the cells at 38-39° C. There is a reasonable expectation of success because Yamanaka discloses a reprogramming method comprising a SeV and Gibco discloses a SeV for reprogramming cells.
Regarding claim 9: Following the discussion of claims 1, 7, and 8 above, Yamanaka et al discloses the reprogramming factor can be introduced into cells using a viral vector such as a Sendai virus. Gibco teaches using a SeV comprising c-Myc which has a temperature sensitive mutation that allows the host cells to be cleared of the SeV and c-Myc. It would have been prima facie obvious to modify the method of Yamanaka et al to use the SeV of Gibco (See rejection of claim 8 above). Furthermore, it would have been prima facie obvious to not include viruses that do not include the temperature sensitive mutation of in the modified method of Yamanaka et al and Gibco because viruses which do not comprise the temperature sensitive mutation would not have been cleared from the cells.
Regarding claims 10 and 11: Following the discussion of claims 1, 7, and 8 above, Yamanaka et al discloses the reprogramming factor can be introduced into cells using a viral vector such as a Sendai virus. The reprogramming method of Yamanaka et al comprises introducing reprogramming factors to cells at 37° C and culturing for 11-29 days which reads on wherein after the reprogramming factor is introduced, the cells are cultured at a temperature lower than the certain temperature for at least two days.
Gibco teaches using a SeV comprising c-Myc which has a temperature sensitive mutation that allows the host cells to be cleared of the SeV and c-Myc by incubating cells at 38-39°C (reads on certain temperature) for 5 days. It would have been prima facie obvious to modify the method of Yamanaka et al to use the SeV of Gibco (See rejection of claim 8 above). Furthermore, it would have been prima facie obvious to perform the 38-39° C incubation step after any of steps (iii-vi) of Yamanaka et al which reads on after the cells are cultured at the temperature lower than the certain temperature, the cells are passaged and cultured at the certain temperature or higher. One would have been motivated to perform the 38-39° incubation step after any of steps (iii-vi) of Yamanaka at all because the cells of steps iii-vi express TRA-1-60 indicating they have been reprogrammed and a person of ordinary skill in the art would have not removed the reprogramming factors prior to the cells being reprogrammed. There is a reasonable expectation of success because Gibco teaches the SeV can be cleared from host cells by increasing the temperature.
Regarding claims 14, 15, 17, and 22: Following the discussion of claim 1 above, Yamanaka discloses in step (v), a plurality of colonies (reads on cells derived from different single cells into which the reprogramming factor is introduced) can be picked up and transferred together in another culture vessel and cultured in bulk which reads on the cells into which the reprogramming factor is introduced are separated/recovered from an incubator, and at least some of the separated cells are mixed and seeded.
Regarding claim 20: Following the discussion of claim 1 above, Yamanaka et al discloses replating the cells into which the reprogramming factor is introduced onto feeder cells. Cells cultured on feeder cells will necessarily be adherent. Therefore, Yamanaka et al discloses an adherent culture.
Regarding claim 23: Following the discussion of claim 1 above, Yamanaka et al discloses reprogramming human dermal fibroblasts.
Regarding claim 27: Following the discussion of claim 1 above, Yamanaka et al discloses the sorted TRA-1-60 positive cells can be cultured in a bFGF-containing culture medium for primate ES cells which reads on the TRA-1-60 positive cells are seeded in a culture medium suitable for culturing iPS cells.
Regarding claim 29: Following the discussion of claim 1 above, Yamanaka et al discloses reprogramming HDF cells in culture medium comprising 10% FBS then replating the cells onto feeder cells after the cells have been transduced. Thus, the reprogramming factor of Yamanaka et al is introduced in a culture absent of feeder cells.
Regarding claim 31: Following the discussion of claims 1 and 5 above, Yamanaka et al discloses using RNA reprogramming factors comprising Oct3/4, Sox2, and Klf4 which reads on a reprogramming factor selected from OCT RNA, SOX RNA, KLF RNA, and MYC RNA.
Claims 1-11, 14-15, 17-20, 22-23, 27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Yamanaka et al (US20160122720A1) in view of Gibco (Reprogramming Fibroblasts with CytoTune, 2012) and Sarafian et al (Stem Cell Research, 2018).
The teachings of Yamanaka et al and Gibco are set forth above.
Yamanaka et al and Gibco render claims 1-11, 14-15, 17, 20, 22-23, 27, and 29 obvious.
Claim 18 and 19 cryopreserving cells: Following the discussion of claim 1 above, Yamanaka et al. discloses a method of producing iPSCs from fibroblasts
Yamanaka et al. does not disclose all the cells or all separated cells are cryopreserved as pluripotent stem cells.
Sarafian et, al. teaches methods of producing and monitoring cell line identity for large quantities of human induced pluripotent stem cells (See abstract). The method of Sarafian et al. includes reprogramming erythroblasts and culturing the cells. Colonies with hiPSC morphology are then pooled and cultured in a 6-well dish. The cells are then cryopreserved (reads on all the cells are cryopreserved) in 9 vials which are used as a SEED BANK (See Fig. 1). One vial is expanded and further cryopreserved (reads on all separated cells are cryopreserved) as 9 vials to constitute a MASTER BANK. Cells from the Master bank are further expanded to constitute a Working bank from which quality control tests can be performed (See Fig. 1). Performing quality control testing is important for cell identification of iPSC cell lines, because iPSC-based research often involves long term culturing, expansion, and differentiation and iPSC cell lines are commonly shared among researchers (See introduction).
Given that Yamanaka et al. and Sarafian et al. both disclose methods of producing iPSCs and Sarafian et al further discloses methods of performing quality control testing on iPSC lines, it would have been prima facie obvious to modify the method of Yamanaka et al. to include the quality control steps of Sarafian, which includes cryopreserving the cells as iPSCs. The motivation to add the quality control steps of Sarafian to the method of Yamanaka et al., would be to expand the cells in order to provide stocks from which quality control testing could be performed because Sarafian et al. teaches quality control is important for cell line identification. There is a reasonable expectation of success because both methods are culturing iPSCs.
Claims 1-11, 14-15, 17, 20-23, 27, 29, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Yamanaka et al (US20160122720A1) in view of Gibco (Reprogramming Fibroblasts with CytoTune, 2012) and Tanabe et al (Wo2018155595A1).
The teachings of Yamanaka et al and Gibco are set forth above.
Yamanaka et al and Gibco render claims 1-11, 14-15, 17, 20, 22-23, 27, 29, and 31 obvious.
Regarding claim 21: Following the discussion of claim 1 above, Yamanaka et al. teaches a method of producing iPSCs by introducing reprogramming factors into fibroblasts. The reprogramming factors can be introduced to the cells using a SeV. The culturing method of Yamanaka et al. comprises culturing the cells on feeder cells.
Yamanaka et al. does not teach a suspension culture.
Tanabe et al. teaches a method for producing pluripotent stem cells. In example 3 of the first embodiment, Tanabe et al. discloses seeding fibroblasts in a suspended gel medium (reads on a suspension culture) and adding Sendai virus expressing the reprogramming factors OCT3/4, SOX2, KLF4, and c-MYC 24 hours after the cells are seeded. The tube was cultured for 23 days and gel medium was added to the tube every 48 hours.
Given that Yamanaka et al. and Tanabe et al. both teach methods of producing iPSCs from fibroblasts which comprise introducing a Sendai virus into the fibroblasts, it would have been prima facie obvious to substitute the culturing method of Yamanaka et al, which comprises culturing in a liquid media on feeder cells, for the culturing method of Tanabe et al. which comprises culturing in a suspension gel media. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable is considered to be obvious. See KSR International Co. V Teleflex Inc 82 USPQ2d 1385 (US2007) at page 1395.
Claims 1-11, 14-15, 17, 20-23, 27, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Yamanaka et al (US20160122720A1) in view of Gibco (Reprogramming Fibroblasts with CytoTune, 2012) and Fujie, et al.(PLOS One, 2014).
The teachings of Yamanaka et al and Gibco are set forth above.
Yamanaka et al and Gibco render claims 1-11, 14-15, 17, 20, 22-23, 27, 29, and 31 obvious.
Regarding claim 30: Following the discussion of claim 1, 7, and 8 above, Yamanaka et al discloses a method of producing iPSCs using a Sendai virus.
Yamanaka et al does not disclose the Sendai virus has a temperature-sensitive mutation selected from the group consisting of TS7, TS12, TS13,TS14, and TS15.
Fujie et al, teaches a method of producing iPSCs. The method uses a TS12KOS (Reads on TS12) Sendai virus vector (SeV) carrying KLF4, OCT 4/4, and SOX2 for generation of iPSCs from human blood cells and human skin fibroblasts (See abstract). The SeV of Fujie et al. has three mutations which cause moderate expression of GFP at 37°C but weak expression at temperatures 38°C and above.
Given that Yamanaka et al discloses a method of producing iPSCs using a SeV and Fujie et al discloses a SeV comprising a TS12 temperature sensitive mutation that allows the host cells to be cleared of the SeV by culturing the cells at 38°C and above, it would have been prima facie obvious to modify the method of Yamanaka et al to use the temperature sensitive SeV of Fujie et al. One would have been motivated to use the SeV of Fujie et al in the method of Yamanaka et al because the SeV of Fujie et al comprises a mutation that allows the host cell to be cleared of vectors by incubating the cells at 38° C or above. There is a reasonable expectation of success because Yamanaka discloses a reprogramming method comprising a SeV and Fujie discloses a SeV for reprogramming cells.
Allowable Subject Matter
Claims 12, 13, and 16 contain subject matter that would be allowable if the claims were rewritten in independent form.
The following is a statement of reasons for the indication of allowable subject matter:
Claims 12, 13, and 16 require the TRA-1-60 positive cells not be isolated, cloned, or colonies of the cells are not picked up. Isolating cells, picking up colonies, and cloning cells are all required steps for clonal expansion of individual colonies of iPSCs. The methods used in the prior art all require a step of picking colonies of iPSCs and further expanding the individual colonies. Specifically, Gibco teaches the step of producing iPSCs that are vector-free requires multiple rounds of expansion from individual iPSC clones. Thus, one would not have expected passaging the cells without picking/isolating colonies and expanding the colonies of iPSCs would produce iPSCs with vector remaining in 4% or less of the iPSCs.
Conclusion
Applicants’ 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 MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
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/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
