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 action is in response to papers filed August 18, 2026. A response to the restriction requirement filed on August 18, 2026 has been acknowledged.
Claims 1, 2, 12, 15, 18, 29, 31-40, 42, 50-54, 57, 62-64, 69-73, 78, and newly added claims 120-121 are currently pending. Applicants’ election without traverse of Group I, e.g. claims 1, 2, 12, 15, 18, 29 and newly added claims 120-121 is acknowledged.
Additionally, Applicants’ election of hydroxamic acid as the species of histone deacetylase inhibitor in the event that Group IX is rejoined for examination is acknowledged. Claims 31-40, 42, 50-54, 57, 62-64, 69-73, and 78 are withdrawn from further consideration, pursuant to 37 CFR 1.142(b), as being drawn to non-elected invention, there being no allowable generic or linking claim. The requirement for the restriction is still deemed proper and is therefore made FINAL.
Therefore, claims 1-2, 12, 18, 29 and 120-121 are currently under examination to which the following grounds of rejection are applicable.
Priority
The instant application claims priority to US Provisional Application 63/470,248, filed June 1, 2023. Therefore, the earliest effective filing date for the instant application is June 1, 2023.
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 1-2, 12, 18, 29 and 120-121 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 1, it is indefinite in its recitation of the phrase “podocyte-like”, as the term fails to clearly define the metes and bounds of the claimed invention. It is unclear to what degree or characteristics of similarity to a podocyte are required for a cell to be regarded as “podocyte-like”.
Although the Specification discloses in paragraph [0054] that “podocyte-like cells refer to engineered podocyte-like cells,” this definition does not resolve the ambiguity. The term “engineered cells” may encompass cells modified by various means, such as genetic modifications, contact, or culture conditions, but the Specification does not provide clear guidance on what properties or markers are necessary for a cell to qualify as “podocyte-like.” Thus, the definition of “podocyte-like cells” in the Specification remains unclear, and the boundaries of the claim are not reasonably certain..
Regarding claim 2, it is indefinite in its recitation of the phrase “dexamethasone”, as it is unclear if the dexamethasone is narrowing the scope of the genus of “corticosteroid” recited in claim 1, or if the media comprises a corticosteroid in addition to a dexamethasone.
Claims 12, 18, 29 and 120-121 are rejected insofar that they depend on claim 1.
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.
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) 1, 2, 12, 18 and 121 are rejected under 35 U.S.C. 103 as being unpatentable over Dai et al. (Published: 2017. Kidney International, 92(6), 1444–1457) in view of Takano et al. (Published: 2007.. Am J Physiol Renal Physiol 292: F1573-F1582) and Yoshimura et al. (Published: 2019. J Am Soc Nephrol. 2019 Feb;30(2):304-321) as evidenced by Little (Cold Spring Harb Perspect Biol. 2012 May 1;4(5):a008300).
Regarding claim 1, Dai teaches that retinoic acid (RA) treatment led to the coexpression of podocyte and parietal epithelial cell markers in a small subset of glomerular cells (parietal epithelial cells (PECs)) in nephritic mice (pp. 1444 col 1, para 1, Abstract and pp. 1447, col 2 para 3). Moreover, after 3 days of incubation with RA, parietal epithelial cells (PECs) were shown to have enhanced expression of podocin, nephrin and synaptopodin (pp. 1448, col 1, para 1; and Figure 5). Dai emphasizes that retinoic acid enhances the transdifferentiation of PECs to podocytes (pp. 1445, col 2 prara 1).
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However, Dai fails to teach culturing glomerular cells in calcitriol or a corticosteroid.
Takano teaches a method of recovering and maintenance of cultured podocytes (pp. 1573, Abstract). Further, Takano teaches that cultured podocytes lose the expression of nephrin (pp. 1573, Abstract) and over time dedifferentiate (pp. 1573, col 1, para 2). However, Takano also states that the addition of 1,25-dihydroxyvitamin D3 (calcitriol), all-trans-retinoic acid or dexamethasone significantly increased activity of the nephrin promoter (Abstract) and recovery of nephrin gene expression in podocytes (pp. 1573, col 2, para 1; pp. 1577, col 1). Takano also suggests that the medium comprising these components may contribute to the differentiation of podocytes (pp. 1577, col 1, para 3).
It would have been prima facie obvious for a person with ordinary skill in the art to culture the PECs of Dai in a culture media comprising retinoic acid, with the addition of dexamethasone (corticosteroid), calcitriol, and more specifically, an all-trans retinoic acid, as taught in Takano, as the art reveals that a culture comprising these substances promotes nephrin expression in podocytes, and it was implied that the a media comprising calcitriol, dexamethasone and retinoic acid contributes to the differentiation of podocytes. Therefore, a person with ordinary skill in the art would reasonably expect that culturing the PECs of Dai in the culture media of Takano would result aid in the differentiation of glomerular cells into induced podocytes, as Dai already discloses that RA promotes the expression of podocyte markers and podocyte cells, and a media further comprising calcitriol and dexamethasone would result in the differentiation of PECs into podocytes with some expectation of success.
Both Dai and Takano fail to teach culturing the cells a second media comprising a SB431542 (hereinafter, “SB”) and an IWR-1-endo, and that the differentiated podocytes display an increased expression of one or more of podocin, nephrin podocalyxin, or synaptopodin, as compared to the glomerular cells prior to culturing in the first media.
Yoshimura teaches a method to cultivate human pluripotent stem cell (PSC)-derived podocytes using different growth factors throughout the three main phases of the podocyte differentiation process, specifically: from nephron progenitor cell (NPC) to peritubular aggregate, from the latter to epithelial renal vesicle (RV), and from RV to podocyte (pp. 304, Abstract). Furthermore, after RV formation, the cells were placed into a culture comprising IWR-1 and SB after 2 days (pp. 307, col 1, para 2). Furthermore, Yoshimura reveals that there was maximal podocyte induction efficiency when culturing the RV formed cells with IWR-1 and SB (pp. 311, col 2). Yoshimura also discloses that under this culture, there was an increased expression in nephrin (Figure 4C) in comparison to the initial treatment with CHIR99021.
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It would have been prima facie obvious for a person with ordinary skill in the art to combine the culture method of Dai, to further comprise culturing the glomerular cells in a second media comprising IWR-1 and SB, as disclosed by Yoshimura, as Yoshimura reveals that the addition of IWR-1 and SB showed maximal induction efficiency for podocytes from epithelial renal vesicle (RV) which are obtained from peritubular aggregates in the development of glomerular podocytes, since renal vesicles give rise to glomerular epithelium, and subsequently podocyte lineages, as evidenced by Little (pp. 11, col 1 para 2). A skilled artisan would have been motivated to implement an additional step of culturing the glomerular cells having epithelial renal vesicles in a second medium comprising IWR-1 and SB to enhance induction efficiency of podocytes with some expectation of success.
Regarding claim 2, the combined teachings of Dai, Takano, Little and Yoshimura render obvious the claimed methodology of claim 1. Moreover, Takano teaches dexamethasone (Abstract).
Regarding claim 12, the combined teachings of Dai, Takano, Little and Yoshimura render obvious the claimed methodology of claim 1. Moreover, Yoshimura teaches that the cells have increased gene expression of NPHS 1 and NPHS 2 (Figure 3F and 4C).
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Regarding claim 18, the combined teachings of Dai, Takano, Little, and Yoshimura render obvious the claimed methodology of claim 1. Moreover, Yoshimura teaches that the induced podocytes have a decreased expression of NPHS1 (nephrin) and NPHS2 (podocin) in comparison to human (primary) adult podocytes (pp. 313 col 1, para 2).
Regarding claim 121, the combined teachings of Dai, Takano, Little and Yoshimura render obvious the claimed methodology of claim 1. Moreover, Yoshimura teaches that the cells were transferred from a medium comprising CHIR99021 and Y27632, to a medium comprising IWR-1, SB and RA, implying that the cells were moved from one medium to another medium (pp. 307, col 1, para 2).
***
Claim(s) 1 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dai et al. (Published: 2017. 92(6), 1444–1457) in view of Takano et al. (Published: 2007.. Am J Physiol Renal Physiol 292: F1573-F1582) and Yoshimura et al. (Published: 2019. J Am Soc Nephrol. 2019 Feb;30(2):304-321) and Little et al. (Cold Spring Harb Perspect Biol. 2012 May 1;4(5):a008300) as applied to claims 1-2, 12, 18 and 121, and in further view of Mundel et al. (Published: 1997. Experimental Cell Research, 236(1), 248–258.).
With regards to claim 1, the combined teachings of Dai, Takano, Yoshimura and Little render obvious the claimed methodology of claim 1.
Dai, Takano and Yoshimura fail to teach wherein the engineered podocyte-like cells comprise a cytoskeletal organization with multiple extensions as compared to a cytoskeletal organization of glomerular cells, as required by claim 15.
Mundel teaches mouse podocyte clones (MPC) and their behaviors regarding cytoskeletal arrangement when they differentiate into mature podocytes, specifically that under nonpermissive conditions, MPC cell growth arrested and induced characteristics of differentiated podocytes (pp. 248, Abstract). Moreover, Mundel found that when these murine podocytes are cultured in nonpermissive conditions (14 days at 37°C), podocytes displayed numerous spindle-like projections (pp. 250, col 1, para 2; FIG 1).
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It would have been obvious for a person with ordinary skill in the art to combine the podocyte culture method of Dai, Takano and Yoshimura, to further comprise the step of culturing the podocytes in nonpermissive conditions, as disclosed in Mundel, as the disclosed culture conditions can induce the characteristics of differentiated mature podocytes, one of the characteristics being the spindle-like projections shown in Figure 1. A person with ordinary skill in the art would reasonably expect that culturing the podocyte cells under Mundel’s culture conditions would yield spindle-like projections, with a reasonable expectation of success.
***
Claim(s) 1, 29 and 120 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dai et al. (Published: 2017. Kidney International, 92(6), 1444–1457) in view of Takano et al. (Published: 2007. Am J Physiol Renal Physiol 292: F1573-F1582) and Yoshimura et al. (Published: 2019. J Am Soc Nephrol. 2019 Feb;30(2):304-321) and Little et al. (Cold Spring Harb Perspect Biol. 2012 May 1;4(5):a008300), in further view of Du et al. (Published: 2016. Cited in IDS Filed 06/14/2024. Adv Healthc Mater. 2016 Aug;5(16):2080-91).
With regards to claim 1, the combined teachings of Dai, Takano, Yoshimura and Little render obvious the claimed methodology of claim 1.
Dai, Takano and Yoshimura fail to teach the the glomerular cells are engrafted onto a decellularized extracellular matrix prior to the culturing glomerular cells in a first media.
Du teaches a method of repopulating a decellularized whole kidney scaffold with native microstructure and extracellular matrix with human-induced pluripotent-stem-cell-derived renal progenitor cells and endothelial cells (pp. 2080, Abstract). Du also found that repopulation of the decellularized tissue helped upregulate genes of renal development within endothelial cells, and aided in general cellular assembly and generating a functioning glomerulus (pp. 2080, Abstract). Furthermore, Du discusses that when the decellularized tissue was repopulated with both renal progenitors and endothelial cells, glomeruli could only be repopulated substantially in the presence of endothelial cells (pp. 2089, col 1, para 2-3; pp. 2085, Figure 5 caption at bottom of page). Du also discusses that extracellular matrix scaffolds could be used to recapitulate organ function (pp. 2080, col 2, par a2-3).
It would have been prima facie obvious for a person with ordinary skill in the art to engraft the glomerular cells of Dai prior to the culturing glomerular cells in a first media, onto the decellularized kidney extracellular matrix of Du, as Du teaches that culturing cells in a decellularized matrix can drive cellular self-assembly, and potentially recapitulate organ function, and potentially the formation of the glomerulus (Abstract). Therefore, a person with ordinary skill in the art would have been motivated to utilize the decellularized kidney scaffold for culturing glomerular cells to promote reorganization within a physiologically relevant environment (pp. 2089, col 2, para 1).
Regarding claim 120, the combined teachings of Dai, Takano, Yoshimura, Little and Du render obvious the claimed methodology. Moreover, Du teaches that the decellularized extracellular matrix is from kidney (pp. 2089, col 2, para 2).
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Katriel B Kasayan whose telephone number is (571)272-1402. The examiner can normally be reached 10-4p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATRIEL BARCELLANO KASAYAN/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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