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 .
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.
Claim Status
Claims 1-11, 16-20 are currently pending and examined on the merits.
Claim Objections
Claims 1, 3, 8, 10, 18-20 are objected to because of the following informalities. Appropriate correction is required.
Claim 1 appears to be missing a colon following “comprising”.
Claim 1 contains an improper capitalization of “Measuring” and “Comparing”.
Claim 3 appears to be missing a comma after “motion bioreactor”.
Claim 8 appears to be missing a colon following “comprising”.
Claim 8 contains an improper capitalization of “Measuring” and “Comparing”.
Claim 8 appears to contain a typographical error and should read “density of[[at]] at least”.
Claim 18 appears to contains a typographical error and should read “wherein the are selected”.
Claim 19 appears to contains a typographical error and should read “wherein the pluripotent stem cells are iPSCs”.
Claim 20 appears to be missing a colon following “comprising”.
Claim 20 contains an improper capitalization of “Measuring” and “Comparing”.
Claim 20 appears to contain a typographical error and should read “density of[[at]] at least”.
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 4, 7-10 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.
Claim 4 contains the limitation “measured inline (in real time)”. It is unclear if the phrase contained within the parentheses is a required limitation of the claim.
Claim 7 contains the limitation “stem cells such as pluripotent stem cells”. It is unclear whether the exemplary limitation is a requirement of the claim or merely optional. See MPEP § 2173.05(d).
Claim 8 recites the limitation "the conversion factor". There is insufficient antecedent basis for this limitation in the claim.
Claim 8 contains the limitation “measuring the permittivity and cell density at at least two different cell densities of a reference suspension culture”. It is unclear if this limitation is indicating that the permittivity and cell density of a single reference suspension culture is measured at two different time points, or if this limitation is indicating that the permittivity and cell density of two different reference suspension cultures is measured.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Justice et al., (2011) Online- and offline- monitoring of stem cell expansion on microcarrier. Cytotechnology, 63: 325-335 (cited on IDS dated 6/7/24, hereinafter Justice).
Regarding claims 1, 8, 20, Justice discloses methods for determining viable cell density by measuring permittivity of the culture (Abstract, Introduction). Justice explains that dielectric spectroscopy is a promising technology for monitoring of cell density in stem cell cultures (Introduction). Justice discloses culturing human mesenchymal stem cells (hMSCs) on RapidCell microcarriers to form cell aggregates (Cell expansion in T-flasks and stirred tank reactor). Permittivity of the cell aggregates is measured at multiple cell concentrations and compared to cell concentrations determined using a hemocytometer (Permittivity measurements, Online permittivity measurement, Fig. 4). Justice explains that the disclosed methods allow for cell density determination of anchorage dependent cells (Conclusions).
Regarding claims 2-3, Justice discloses that the culture is performed in a 2 L stirred bioreactor system (Cell expansion in T-flasks and stirred tank bioreactor).
Regarding claim 4, Justice discloses that cells grown on microcarriers are monitored by throughout the whole cultivation time (i.e., in-line monitoring) (Permittivity measurements).
Regarding claims 5-6, Justice discloses measuring permittivity using a dielectric spectroscopy probe (Permittivity measurements
Regarding claim 7, Justice disclose that the cells are human mesenchymal stem cells (hMSCs) (Cell expansion in T-flasks and stirred tank reactor).
Regarding claim 9, Justice discloses that cell concentrations are calculated from known growth kinetics and correlated to fluorescence intensity in a linear correlation (Online fluorescence assay, Online permittivity measurement, Figs. 3-4).
Regarding claim 10, Justice discloses using hMSCs for both reference and aggregate culture (Cell expansion in T-flasks and stirred tank reactor, Permittivity measurements).
Regarding claim 9, Justice discloses that cell concentrations are calculated from known growth kinetics and correlated to fluorescence intensity in a linear correlation (Online fluorescence assay, Online permittivity measurement, Figs. 3-4).
Regarding claim 11, Justice explains that viable cells remain adherent on the carrier, such that they reflect the viable cell concentration (Online fluorescence assay).
Therefore, every limitation of claims 1-11 is present and the subject matter is anticipated.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claim(s) 17-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Justice as applied to claims 1-11 above.
Regarding claims 17-19, Justice does not explicitly disclose that the cells are pluripotent stem cells, such as induced pluripotent stem cells. However, Heilman explains the disclosed methods are highly useful for the monitoring expansion processes of stem cells generally. Therefore, there is a suggestion present in Justice that the disclosed methods may be useful in monitoring of other stem cell types. A skilled artisan would understand that well-known stem types, such as iPSCs, could be substituted into the methods of Justice as suggested.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Justice as applied to claims 1-11 above, and further in view of Heilman et al., (2017) Dielectric spectroscopy platform to measure MCF10A epithelial cell aggregation as a model for spheroidal cell cluster analysis. Royal Society of Chemistry, 142:1601-1607 (hereinafter Heilman).
Regarding claim 16, Justice does not disclose that the cell are not in a microcarrier culture.
Heilman discloses methods of monitoring cell aggregates for cell position, density, and morphology using dielectric spectroscopy (Abstract, Introduction). Heilman explains that cell aggregates have been demonstrated to be relevant 3D cell culture models such that non-invasive monitoring techniques would be highly advantageous (Introduction). Heilman discloses 3D culturing MCF10A epithelial cells in aggregate without the use microcarriers (Cell aggregate assay). Dielectric spectra of the cell aggregates is compared to a control (Dielectric spectroscopy). Heilman concludes that the disclosed methods allow for monitoring cell density, cell migration and, tissue morphology in cell aggregates (Conclusion).
As both Justice and Heilman are directed to methods of monitoring cell aggregates using dielectric spectroscopy, it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would be motivated to utilize a microcarrier free carrier in the methods of Justice as Heilman explains that cell aggregates are a highly relevant cell culture model.
Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Párta et al., (2014) Application of dielectric spectroscopy for monitoring high cell density in monoclonal antibody producing CHO cell cultivations.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA D JOHNSON whose telephone number is (571)270-1414. The examiner can normally be reached Monday-Friday 8:00-4:00 CT.
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/KARA D JOHNSON/Primary Examiner, Art Unit 1632