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 .
DETAILED ACTION
This application is now under examination by Valarie Bertoglio, AU 1632.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/11/2025 has been entered.
Status of the Claims
Claims 1-4, 6, 7, and 9-14 are currently pending.
Claims 5 and 8 are canceled.
Claims 9-11 are withdrawn from further consideration.
Claims 1-4, 6, 7 and 12-14 have been considered on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 6, 7 and 12-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date.” See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).”
In the instant case the claimed renal cells expressing the newly recited markers encompassed by the claims lack a written description. The specification fails to describe what renal cell types fall into this genus of cells that form aggregates in culture and maintain expression of the recited markers though freeze/thaw, other than renal proximal tubule epithelial cells. It was unknown as of Applicants' effective filing date that any renal cell types would have the property of aggregation of cells and maintenance of marker expression as claimed, following freeze thaw.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
Claim Rejections - 35 USC § 112
The claim rejection under 35 USC § 112(b) is maintained and repeated below. A new claim rejection is added.
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.
The previous rejection of claims 1-4, 6, 7, 12-14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
Claims 1-4, 6, 7 and 12-14 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.
In claims 1 and 14, the limitation “wherein the culture vessel is subjected to a cell non-adhesion process” is not clear if that process is intended to be an active step in the claim or is limiting the culture vessel to one that has already undergone that process. Claims 2-4, 6, 7, 12-13 depend from claim 1.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1,2,3,6,12 and 14 remain rejected under 35 U.S.C. 102(a)(2) as being anticipated by Shrivastava et al. (WO 2020/041065 A1).
Regarding claims 1 and 14, Shrivastava discloses methods for producing cellular spheroids, wherein the cells are epithelial cells that can be kidney epithelial cells and can also be cells of the interior of a renal tubule (renal cells) (see whole document; pg. 13, par. 2; pg. 9, par. 2). The epithelial cells are cultured as aggregates and are then recovered to be cultured in suspension to prevent adherence to the culture vessels, where the aggregates grow into spheroids and are cultured for at least 3 months (over 7 days or more) (pg. 72, par. 2-4; pg. 73, par. 1). The spheroids are cryopreserved (frozen while an aggregated state is substantially maintained), thawed, and are cultured in suspension for at least two weeks (7 days or more) after thawing, maintaining mature function (pg. 73, par. 3). The culture vessel is a low-attachment container that contains a coating to inhibit the cultured cells from attaching or adhering to the surface of the container (subjected to a cell non-adhesion process or made of a cell non-adhesive material) (pg. 32, lines 29-33; pg. 47, lines 3-8). Regarding claim 14, the recovered cultured renal cells are cryopreserved in liquid nitrogen storage (pg. 73, line 25). The instant specification discloses that a liquid nitrogen storage vessel is at -150°C or less [0035]. Therefore, the renal cells are frozen to below a temperature that the renal cells are frozen or under low temperatures at which the renal cell can freeze.
With regard to the newly added marker gene expression requirement, Shrivastava teaches epithelial cells express the tight junction protein ZO-1 and adherens junction protein E-cadherin and these proteins are indicators of cell aggregation. Thus, it is held that if the cells are present as an aggregate, it is inherent that they will express E-cadherin and ZO-1 at least at a level of 10% of whare is found in vivo.
Regarding claim 2, the spheroids are cryopreserved with PneumaCult™-ALI medium with 1 μM A83-01 and 5 μM Y-27632 (P+A+Y) +10%FBS +10%DMSO (cryopreservation solution) and liquid nitrogen (pg. 73, par. 3). Regarding claim 3, Shrivastava’s aggregates are formed by aggregating 50 to 200 cells, or more than 200 cells (100 or more and 5000 or less) (pg. 24, par. 2). Regarding claim 6, in some embodiments the epithelial cells comprise human primary cells (pg. 12, par. 2; pg. 5, par. 2; pg. 14, par. 2; pg. 38, par. 5). Regarding claim 12, the cell non-adhesion process comprises use of a cell non-adhesive hydrogel coating (pg. 47, lines 7-8).
Therefore, Shrivastava anticipates the subject matter disclosed above.
Applicant argues Srivastava doesn’t teach non-adherent culture of the thawed aggregates for over 7 days. Applicant is directed to page 73 of Srivastaca where it is stated:
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The marker gene limitation is addressed above.
Claim Rejections - 35 USC § 103
The following rejections under 35 USC 103 are. maintained Applicant references the arguments relating to the teachings of Srivastava, which were not persuasive, as set forth above.
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.
Claim 4 remains rejected under 35 U.S.C. 103 as being unpatentable over Shrivastava et al. (WO 2020/041065 A1) (ref. of record), in view of Hubel et al. (WO 2020/223125 A1, 2020) (ref. of record).
The teachings of Shrivastava can be found in the rejection above.
While Shrivastava discloses cryopreserving the spheroids, Shrivastava fails to disclose freezing the cells by slow freezing, as recited in claim 4. However, Hubel remedies Shrivastava’s deficiency.
Hubel discloses a method for cryopreserving a variety of cells including renal cells and kidney organoids (see whole document). Hubel recovered cultured aggregates and cryopreserved them while maintaining an aggregated state [0040-0045]. Claim 4 recites “the renal cells are frozen by slow freezing in the freezing step”. The instant specification discloses that “Slow freezing refers to a method in which cells are frozen while the rate of temperature-drop of the cells to be frozen is adjusted to a predetermined range so that the cells are gradually frozen” and further provides examples of rates of temperature drop of cells during freezing of about 0.2°C to about 3°C per minute, and 1°C per minute [0030]. Hubel teaches using controlled-rate freezing, which is programmed to followed a defined and consistent cooling profile, and further teaches cooling rates of 0.2 °C/min or greater, 0.3 °C/min or greater, 0.4 °C/min or greater, 0.5 °C/min or greater, 0.8 °C/min or greater, 1.0 °C/min or greater [0042; 0062]. Accordingly, Hubel teaches freezing the cells by slow freezing in the freezing step.
In addition, Hubel discloses that conventional slow cooling typically implies using a solution of 10% DMSO, which is known to be toxic to cells, can alter the epigenetics and forces users to freeze the cells quickly after introduction of the solution to minimize exposure time to DMSO [0036-0038]. Hubel continues explaining that this requirement influences workflow, making it more difficult and more expensive to preserve the cells [0038].
Therefore, it would have been obvious to a person of ordinary skill in the art to freeze the renal cells by slow freezing as recited in claim 4 and as disclosed by Hubel since there were known disadvantages of practicing conventional cooling using DMSO, as explained by Hubel. A person of skill in the art would have been motivated to substitute the method of freezing the cells using DMSO as disclosed by Shrivastava with Hubel’s controlled-rate or slow cooling method with the purpose of gradually freezing the cells, avoiding toxicity and epigenetic changes, and overall improving the workflow while performing cryopreservation of the cells. Furthermore, a skilled artisan would have had a reasonable expectation of success since methods of generating renal cell aggregates and cryopreserving them for future uses were known and practiced before the effective filing date, as taught by Hubel.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Claim 7 remains rejected under 35 U.S.C. 102(a)(2) as being unpatentable over Shrivastava et al. (WO 2020/041065 A1).
The teachings of Shrivastava can be found in the previous rejections above.
Regarding claim 7, Shrivastava discloses epithelial cells that can be kidney epithelial cells (renal cells) and that can also be cells of the interior of a renal tubule (pg. 9, par. 2). However, Shrivastava fails to explicitly disclose that the renal cells are proximal tubule-derived cells.
Nonetheless, since Shrivastava teaches that the epithelial cells can be cells of the interior of a renal tubule, a person of ordinary skill in the art would expect proximal tubular epithelial cells or proximal tubule-derived cells, which are epithelial cells of the interior of a renal tubule, to be included in Shrivastava’s disclosure and thus, can be cultured according to the method disclosed by Shrivastava.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Claim 13 remains rejected under 35 U.S.C. 103 as being unpatentable over Shrivastava et al. (WO 2020/041065 A1) (ref. of record) in view of Kitagawa (US 2020/0032216 A1) (ref. of record).
The applied reference (Kitagawa) has a common Applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
The teachings of Shrivastava can be found in the rejections above.
Regarding claim 13, Shrivastava does not teach glass, low-density polyethylene, medium-density polyethylene, polyvinyl chloride, polyethylene-vinyl acetate copolymer, poly(ethylene-ethylacrylate) copolymer, poly(ethylene-methacrylate) copolymer, or poly(ethylene-vinylacetate) copolymer as a cell-non-adhesive material.
However, Kitagawa teaches a method of cultivating kidney cells in a state of being non-adherent to a culture vessel that has been subjected to a non-cell adhesion treatment or is formed from a non-cell-adhesive material such as low-density polyethylene, medium-density polyethylene, polyvinyl chloride, polyethylene-vinyl acetate copolymer, poly(ethylene-ethylacrylate) copolymer, poly(ethylene-methacrylate) copolymer, or poly(ethylene-vinylacetate) copolymer (abstract; [0093]).
Accordingly, it would have been obvious to one of ordinary skill at the effective filing date of the claimed invention to combine the teachings of Shrivastava regarding a method of culturing renal cell aggregates and spheroids under low adherent conditions with the teachings of Kitagawa regarding non-adherent kidney (renal) cell culture on a culture vessel made of a non-adhesive material to arrive at the claimed invention since Kitagawa provides an alternative method for achieving non-adherent culture conditions to obtain renal cell aggregates, and a skilled artisan looking to optimize or modify the culture method of Shrivastava would have been motivated to use a culture vessel made of the claimed polymer materials to achieve non-adherent conditions using a known approach, therefore, yielding predictable results. Furthermore, a person of ordinary skill in the art would have had a reasonable expectation of success since both references teach non-adherent renal cell culture using known methods, and using the culture vessels made of the polymer materials taught by Kitagawa to culture the cells with the culture method as taught by Shrivastava would have been expected to produce predictable results without undue experimentation.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632