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 .
Claims 1-10 and 17-27 are pending in this application, Claims 2 and 22-26 are acknowledged as withdrawn, Claims 1, 3-10, 17-21 and 27 were examined on their merits.
The objection to the Specification because the abstract of the disclosure
because it is too short to describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details has been withdrawn due to the Applicant’s amendment to the Specification filed 06/16/2026.
The objection to the Specification due to the improper use of Trademarks has been withdrawn due to the Applicant’s amendment to the Specification filed 06/16/2026.
The objection to the Specification due to the presence of non-English language subject matter has been withdrawn due to the Applicant’s amendment to the Specification filed 06/16/2026.
The rejection(s) of Claims 7, 17 and 19-21 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inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, has been withdrawn due to the Applicant’s amendment to the claims filed 06/16/2026.
Specification
The replacement abstract of the disclosure filed 06/16/2026 does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
Claim Rejections - 35 USC § 103
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, 3-9, 17-21 and 27 are rejected under 35 U.S.C. § 103 as being
unpatentable over Kropp et al. (2017) in view of Varecka et al. (WO 90/11345), both cited in the IDS.
Kropp et al. teaches the expansion of human pluripotent stem cells (hPSC) aggregates, wherein hPSC include human embryonic (hESC) and induced pluripotent (hiPSC) stem cells (Pg. 245, Column 1, Section 1.1, 1st paragraph) in suspension/perfusion culture within a stirring bioreactor under conditions that allow proliferation of the stem cells (Pg. 248, Table 1), and performing medium exchange on the perfusion culture either inside or outside a bioreactor (Pg. 250, Fig. 3D), and reading on Claims 1, 3, 4, 6, 9, 17, 20 and 21.
The teachings of Kropp et al. were discussed above.
Kropp et al. did not teach a method wherein the medium exchange is performed through a rotating mesh/spin filter, as required by Claims 1 and 5;
wherein the spin filter has a pore size of about 10 µm, as required by Claims 7 and 27;
wherein the spin filter is attached to the stirrer or stirring rod of the bioreactor, as required by Claim 18;
or wherein a device housing the spin filter is fluidly coupled with the bioreactor to form a closed system, as required by Claim 19.
Varecka et al. teaches a method wherein medium is removed from a perfusion culture by a spin filter (rotating mesh) attached to a stirring rod (Fig. 1, #107) and fluidically coupled to the bioreactor to form a closed system (Pgs. 13-14, Claim 6 and Fig. 1);
wherein the filter has pores/apertures of from about 5-10 µm (encompassed within or overlapping the claimed pore size ranges) (Pg. 8, Lines 21-22);
wherein the use of the spin filter enables withdrawal of substantially cell-free medium from the suspension culture vessel while at the same time being less susceptible to clogging and fouling such that it can remain in operation for extended periods of time at reasonably high cell densities and perfusion rates, thereby enabling suspension culture of cells to the high densities required for commercial-scale production of cell-secreted proteins (Pg. 4, Lines 9-17).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of expanding hPSC cells in perfusion culture of Kropp et al. with the use of a perfusion bioreactor comprising a spin filter as taught by Varecka et al. because this would provide a means to remove/replace cell medium with advantages over the static filter of Kropp. Those of ordinary skill in the art would have been motivated to make this modification in order to remove spent media with less clogging/fouling allowing the bioreactor to remain in operation for extended periods of time at reasonably high cell densities and perfusion rates, thereby enabling suspension culture of cells to the high densities required for commercial-scale production of cell-secreted proteins.
There would have been a reasonable expectation of success in making this modification because both references are reasonably drawn to the same field of endeavor, that is, the perfusion culture of suspended cells.
With regard to Claim 8, Kropp et al. teaches that cell aggregates exceeding (a diameter) of about 300 µm is to be avoided as this is known to result in cell necrosis due to limited nutrient and gas diffusion into the aggregate center (Pg. 247, Column 2, Section 3.2.2, 2ⁿᵈ paragraph). Thus, the diameter of the hPSC cell aggregates is a recognized result-effective variable. Therefore, the determination of the optimal or workable ranges of the hPSC aggregate diameter by routine experimentation and optimization of result effective variables is not inventive. In this instance, the hPSC aggregate diameter must be kept below a certain range to avoid cell necrosis. Those of ordinary skill in the art before the effective filing date on the instant invention would have been motivated to make this modification in order to obtain cell aggregates without cell death. There would have been a reasonable expectation of success in making this modification because the reference already teaches an upper limit of a cell aggregate range and the determination of result effective variables (e.g. a specific hPSC aggregate diameter) by routine optimization and experimentation is within the purview of those of ordinary skill in the art.
Claims 1, 3-9, 10, 17-21 and 27 are rejected under 35 U.S.C. § 103 as being unpatentable over Kropp et al. (2017), in view of Varecka et al. (WO 90/11345), both cited in the IDS, as applied to Claims 1, 3-9, 17-21 and 27 above, and further in view of Germeroth (WO 2020/012033 A1), of record.
The teachings of Kropp et al. and Varecka et al. were discussed above.
Neither reference taught a method wherein the stem cells are selected from
the group consisting of TC-1133, the Human Episomal iPSC Line of Gibco ATCC ACS-
1004, ATCC ACS-1021, ATCC ACS-1025, ATCC ACS-1027, ATCC ACS-1030, as
required by Claim 10.
Germeroth teaches that pluripotent stem cells (PSC) refers to cells that are able
to differentiate into every cell type of the body, the most utilized PSC are embryonic
(ESC) and induced pluripotent (iPSC) stem cells, and exemplary iPSC cell lines
include ATCC ACS-1004, ATCC ACS-1021 , ATCC ACS-1025, ATCC ACS-1027 or
ATCC ACS-1030 (Pgs. 11-12, Paragraph [0052]).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of Kropp et al. and Varecka et
al. of cultivating hPSC, such as hESC and hiPSC, in a perfusion culture bioreactor
comprising a spin filter media exchanger to use the specific iPSC of Germeroth because
Kropp is generally drawn to the culture of PSC cells and Germeroth provides specific
iPSC cell lines which are suitable for culturing. Those of ordinary skill in the art would
have been motivated to make this modification in order to culture specific iPSC cell
types, as desired. There would have been a reasonable expectation of success in
making this modification because Kropp teaches the culture of non-specific PSC and
Germeroth teaches specific iPSC which are suitable for culturing.
Response to Arguments
Applicant’s arguments, see Remarks, filed 06/16/2026, with respect to the above withdrawn objections/rejection have been fully considered and are persuasive.
The Applicant's remaining arguments filed 06/16/2026 have been fully considered but they are not persuasive with regard to the pending rejections above.
The Applicant argues that there would not have been a reasonable expectation of success in modifying the hPSC perfusion culture of Kropp with the spin filter of Varecka.
Applicant notes that Varecka discloses the spin filter to perform media exchange from perfusion culture in conventional cell suspension cultures, however hPSC are sensitive to mechanical (shear) stress, as acknowledged by Kropp, which could negatively affect cell health/viability. Applicant concludes that the ordinary artisan would not have reasonably expected that a spin filter medium exchanger could be used with hPSC culture (Remarks, Pg. 12, Lines 15-29 and Pg. 13, Lines 1-11).
This is not found to be persuasive for the following reasons, the fact that the spin filter medium exchanger could “potentially” cause negative effects on an hPSC cell culture is not evidence that it will do so, or in any way, a teaching away from doing so. The Examiner maintains that there would have been a reasonable expectation of success in making this modification because both the Kropp and Varecka references are reasonably drawn to the same field of endeavor, that is, the perfusion culture of suspended cells.
The Applicant argues that Kropp teaches only a few studies had been performed on perfusion culture of PSC and only identified a single published example which does not utilize a spin-filter as claimed. Applicant concludes that the skilled artisan would understand the need to avoid imposing mechanical stress on PSC culture and would not therefore have looked to a spinning mesh filter in such a culture. Applicant notes that Claims 8 and 10 are non-obvious for the reasoning provided above (Remarks, Pg. 13, Lines 13-28 and Pg. 14).
This is not found to be persuasive for the following reasons, the fact that perfusion culture was not widely used for PSC cultivation is not evidence that a spin filter medium exchanger used with the culture would cause negative effects on the hPSC cell culture or in any way, a teaching away from doing so. The Examiner notes that Kropp (nor any of the references it cites) was not cited for any teaching of a spin filter medium exchanger. The Examiner notes that the Applicant cited “Weegman” reference is not listed in the citations of Kropp. The Examiner maintains that there would have been a reasonable expectation of success in making this modification because both the Kropp and Varecka references are reasonably drawn to the same field of endeavor, that is, the perfusion culture of suspended cells. Claims 8 and 10 are found to be obvious for the reasoning provided in the above rejections.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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