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 .
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1, 3-10 and 17-21) in the reply filed on 02/17/2026 is acknowledged. Claims 2 and 22-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/17/2026.
Claims 1, 3-10 and 17-21 were examined on their merits.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to 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. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The use of the terms SARTORIUS™, UNIVESSEL™, STEMFLEX™, PLURISTEM™, STEMMACS™, NUTRISTEM™, STEMFIT™ and NUCLEOCOUNTER™ which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because of the following informalities: the Specification, Pg. 17, Paragraph [0072] contains material in the German language. Appropriate correction is required.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the Examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7, 17 and 19-21 are 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.
Regarding Claim 7, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 17, 18, 19 and 20&21 respectively recite the limitations; "the bioreactor", “the spin-filter” & “the stirrer”, “the device” and “the pluripotent stem cells”. There is insufficient antecedent basis for these limitations in the claims.
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, 4, 6, 7, 9 and 17-21 are rejected under 35 U.S.C. § 103 as being unpatentable over Kropp et al. (2017), cited in the IDS, in view of Varecka et al. (WO 90/11345), 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 no 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 Claim 7;
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, 4, 6, 7, 9, 10 and 17-21 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, 4, 6, 7, 9 and 17-21 above, and further in view of Germeroth (WO 2020/012033 A1).
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.
No claims are allowed.
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 03/05/2026