DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s Response to Election/Restriction Filed, Amendment, and Arguments/Remarks, filed 08 July 2026, have been entered. Claims 1, 4-7, 11-13, 17, 21-23, 26-27, and 32 were previously pending in the application. Applicant canceled no claims and added no new claims. Claims 1, 4-7, 11-13, 17, 21-23, 26-27, and 32 are currently pending. Claims 1, 26, 27, and 32 are independent claims. Applicant’s election without traverse of the invention of Group I, drawn to a method for producing podocytes and a composition comprising podocytes produced by the method, is acknowledged.
Claims 27 and 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 4-7, 11-13, 17, 21-23, and 26 are currently pending in the application and under examination to which the following grounds of rejection are applicable. An action on the merits follows.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2022/075447, filed 25 August 2022, which claims priority to U.S. Provisional Application No. 63/237,363, filed 26 August 2021.
Thus, the earliest possible priority for the instant application is 26 August 2021.
Information Disclosure Statement
The three information disclosure statements filed 13 August 2024 have been considered by the Examiner.
Specification
The disclosure is objected to because of the following informalities: the Brief Description of the Drawings recites panels Figure 14G and 14H. However, the Drawings only present Figures 14A-F without a G or H panel. Appropriate correction is required.
The use of the terms “Geltrex”, “Matrigel”, “Cryostor” on page 24; “Accutase” on page 26; “Matrigel”, “DMEM”, “GlutaMax”, “Accutase” on page 35, “DMEM”, “GlutaMax” on page 36, “FACSCanto II” on page 37, “PhosStop”, “iBlot”, “milli-Q”, “Odyssey”, “ZOE”, “RNeasy” on page 39, “SYBR Green” on page 40, “CytoTox”, “DMEM” on page 42, which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
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.
Note that the specification has not been inspected sufficiently to identify all instances of trade names and/or marks used in commerce. It is Applicant’s responsibility to ensure complete compliance.
Claim Objections
Claim 1, 4-7, 11-13, 17, 21-23, and 26 are objected to because of the following informalities: claim 1 recites, “culturing the intermediate mesodermal cells of claim 1” and “culturing the nephron progenitor cells of claim 2”. Claims cannot depend upon themselves. Additionally, claim 2 is cancelled, and therefore, the actual method steps which Applicant intends to claim as part of the invention of claim 1 cannot be determined. Further, claims 4-7, 11-13, 17, 21-23, and 26 depend upon or encompass claim 1, and incorporate all of the limitations of claim 1. As such, the actual method steps which Applicant intends to claim as part of the invention of claims 4-7, 11-13, 17, 21-23, and 26 likewise cannot be determined. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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, 4-7, 11-13, 17, 21-23, and 26 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 1 has multiple issues of indefiniteness.
Claim 1 recites the limitation "the human pluripotent stem cells" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites, “comprising Activin A and/or Noggin and a glycogen synthase kinase 3 (GSK3) inhibitor and/or Wnt3a”, which is indefinite because it is unclear how the mix of “and/or” and “and” are meant to group the alternative options. For example, it is unclear whether Applicant intends to claim (Activin A and/or Noggin) and (a GSK3 inhibitor and/or Wnt3a) or whether Applicant intends to claim Activin A and/or (Noggin and a GSK3 inhibitor) and/or Wnt3a.
Claim 1 recites, “the intermediate mesodermal cells of claim 1”, which is indefinite because by reciting “of claim 1”, claim 1 is referring to itself, and therefore the claim limitation is recursive. Additionally, claim 1 is directed to a method of producing podocyte and not directed to intermediate mesodermal cells. Further, a claim cannot depend on itself. See MPEP 608.01(n)(III), which states that a proper dependent claim must reference a claim previously set forth such that a claim in dependent form shall be construed to incorporate by reference all limitations of the claim to which it refers.
Claim 1 additionally recites, “culturing the nephron progenitor cells of claim 2”. However, claim 2 is cancelled, and, therefore, claim 1 is indefinite because the actual method steps which Applicant intends to claim as part of the invention of claim 1 cannot be determined. Also, claims 4-7, 11-13, 17, 21-23, and 26 are dependent on and/or encompass claim 1, and thus incorporate all the limitations of claim 1 and are likewise indefinite due to the dependency on the cancelled claim. See MPEP 608.01(n)(V) which states that if the base claim has been cancelled, a claim which is directly or indirectly dependent thereon should be rejected as incomplete.
As such, the metes and bounds of the claims cannot be determined.
In the interest of compact prosecution, claim 1 has been interpreted such that “the intermediate mesodermal cells of claim 1” in line 8 are any intermediate mesodermal cells and “the nephron progenitor cells of claim 2” in line 11 are any nephron progenitor cells.
Claim 4 recites the limitation, “the GSK3 inhibitor” in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 4 is dependent on claim 1. Claim 1 has multiple recitations of “a glycogen synthase kinase 3 (GSK3) inhibitor” or “a GSK3 inhibitor” in lines 3, 6, and 13, and thus is it unclear which GSK3 inhibitor claim 4 is referencing. As such, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 26 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim(s) recite(s) a composition comprising podocytes produced by the method of claim 1.
This judicial exception is not integrated into a practical application because the product is merely any composition comprising podocytes without reciting any additional elements. Although the podocytes are produced by the method of claim 1, the method of claim 1 is merely culturing human pluripotent stem cells in culture media to induce a stepwise differentiation into podocytes, wherein the culture media comprises factors (i.e., GSK3 inhibitor, Activin A, FGF9, BMP7, Wnt3a, Noggin, heparin, VEGF, and/or retinoic acid) which are or encompass factors naturally occurring in organisms during the natural differentiation process and affect the structure of the cells (e.g., gene expression) to achieve structural changes which are naturally a part of the natural differentiation process. Additionally, therapeutically useful non-recombinant cells are fundamentally intended to mimic healthy natural podocytes for transplantation and/or are meant to mimic naturally occurring diseased podocytes as a model to study naturally occurring kidney diseases. For example, Qian teaches that in vitro differentiated podocytes adopt podocyte morphology, express canonical podocyte markers, and exhibit podocyte phenotypes for use in in vitro modeling of podocyte development and disease or for cell therapies, wherein s source of human podocytes exhibiting key phenotypes of healthy and diseased podocytes is a valuable tool for advancing kidney research and developing treatments for chronic kidney disease [Qian et al. 2019, Scientific Reports, 9:2765, 1-12, IDS, abstract, pg 1 ¶ 2]. Accordingly, the podocytes of claim 26 are not distinct from naturally occurring human podocytes.
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional elements are recited in the product of claim 26 comprising the podocytes produced by the method of claim 1. As such, no additional elements are adding significantly more to the exception.
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, 4-7, 11-13, 17, 21-23, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Ingber [US20160143949A1, published 26 May 2016] in view of Takasato [US20190032020A1, published 31 January 2019].
Regarding claims 1 and 4, Ingber teaches a method for producing podocytes, the method comprising (a) culturing human pluripotent stem cells in a primitive streak induction medium/ Stage 1 medium comprising Activin A and a glycogen synthase kinase 3 (GSK3) inhibitor, CHIR99021, to produce posterior primitive streak cells [Figure 1A, 3A]; (b) culturing the posterior primitive streak cells in an intermediate mesoderm induction medium/ Stage 2 medium comprising the GSK3 inhibitor CHIR99021 to produce intermediate mesodermal cells (IMCs) [Figure 1A, 3A]; and (d) culturing the intermediate mesodermal cells in a podocyte induction medium comprising bone morphogenic protein 7 (BMP7), vascular endothelial growth factor (VEGF), the GSK3 inhibitor CHIR99021, retinoic acid, and Activin A to produce podocytes [Figure 1A, 3A].
Ingber does not teach incubating the intermediate mesodermal cells in a nephron progenitor induction medium comprising fibroblast growth factor 9 (FGF9) and heparin to produce nephron progenitor cells (NPCs) enroute to producing the podocytes.
However, Takasato teaches culturing intermediate mesodermal cells in a nephron progenitor induction medium comprising FGF9 and heparin to produce nephron progenitor cells, wherein FGF9 and heparin alone are capable of facilitating differentiation of hiPSC/hPSC-derived intermediate mesoderm into nephron progenitor cells, and wherein a combination of FGF9 and heparin is a particularly preferred embodiment [0005, 0055, 0127-0130]. Takasato also teaches that heparin is typically included to promote or enhance the biological activity of fibroblast growth factors such as the preferred FGF9 [0069].
Therefore, given the teachings of Takasato that differentiating intermediate mesoderm cells into nephron progenitor cells in a medium comprising FGF9 and heparin is a particularly preferred embodiment for generating NPCs from IMCs, an ordinarily skilled artisan at the time of filing the instant application would have been motivated to differentiate intermediate mesoderm cells into nephron progenitor cells in a medium comprising FGF9 and heparin.
Regarding claims 5-6, Ingber teaches in some embodiments, the first mesoderm differentiation medium/ primitive streak induction medium further comprises a ROCK inhibitor, specifically Y-27632 [0150, 0153, Table 1].
Regarding claim 7, Ingber teaches wherein the first mesoderm differentiation medium/ primitive streak induction medium comprises about 10 µM Y-27632, about 100 ng/ml Activin A, and about 3 µM CHIR99021 [0377, Table 1]. Ingber also teaches wherein the second mesoderm differentiation medium/ intermediate mesoderm induction medium comprises about 0.1 µM to about 10 µM CHIR99021 [0029, 0157]. Ingber teaches wherein the podocyte induction medium comprises about 100 ng/mL BMP-7, 50 ng/mL VEGF, 3 µM CHIR99021, 0.1 µM retinoic acid, and 100 ng/mL Activin A [0380, Table 3]. Ingber also teaches wherein the term “retinoic acid” generally refers to a naturally occurring retinoic acid or a derivative thereof [0108].
Additionally, Takasato teaches wherein the nephron progenitor induction medium comprises 200 ng/mL FGF9 and 1 µg/mL heparin [0238]. Takasato also teaches wherein the retinoic acid is all-trans retinoic acid [0066].
Regarding claims 11-12, Ingber teaches wherein the pluripotent stem cells, mesodermal cells, and/or intermediate mesodermal cells are cultured under adherent conditions on a surface coated with laminin [0164]. Although Ingber teaches wherein the pluripotent stem cells or intermediate mesodermal cells can be co-cultured with other cell types [0168], Ingber does not teach wherein any of the pluripotent stem cells, posterior primitive streak cells, intermediate mesodermal cells, nor nephron progenitor cells are cultured in the presence of feeder cells, and therefore, absent evidence to the contrary, the culturing of Ingber is presumed to be carried out on a feeder free culture plate.
Regarding claim 13, Ingber teaches assaying the posterior primitive streak cells produced by culturing with the first mesoderm differentiation medium for MIXL1 expression [0015, 0124]. Ingber also teaches assaying the intermediate mesodermal cells produced by culturing with the second mesoderm differentiation medium for PAX8 expression [0016, 0124]. Ingber further teaches assaying the podocytes produced for synaptopodin (SYNPO), podocalyxin (PODXL), and/or nephrin expression [0124, 0143].
Takasato teaches assaying the nephron progenitor cells for expression of SIX2 and/or CITED1 [0072, 0122, 0124].
Regarding claim 17, Ingber teaches wherein the culturing the human pluripotent stem cells in the stage 1 medium is for about 1 to about 5 days, about 1 to about 3 days, no more than 4 days, and specifically 2 days to produce the posterior primitive streak cells [0019, 0141, Figure 1A, 3A]; the culturing the posterior primitive streak cells in the stage 2 medium is for about 3 days to about 30 days to produce intermediate mesoderm cells [0020, 0142, Figure 3A]; and the culturing cells in the podocyte induction medium is for about 1 day to 1 week, about 2 days to about 10 days, about 3 to about 5 days, no more than 7 days, or specifically 5 days to produce podocytes [0011, 0014, 0021, 0143, Figure 1A, 3A].
Takasato teaches wherein the intermediate mesoderm cells are cultured for about 3 days to produce nephron progenitor cells [0141, 0238-0241].
Regarding claim 21, Ingber teaches wherein the pluripotent stem cells are contacted with the podocyte induction medium until the cells differentiate into post-mitotic podocytes, wherein the contact period can range from about 7 to 10 days [0123].
Regarding claims 22-23, Ingber teaches wherein the pluripotent stem cells are induced pluripotent stem cells (iPSCs) [0122, 0125, 0210, 0247] and wherein the iPSCs are genetically modified to model genetic kidney disease [0044, 0192, 0211-0213].
Regarding claim 26, Ingber teaches a composition comprising podocytes produced by the method of differentiating human pluripotent stem cells into podocytes [0187, 0200].
Given the motivation taught by Takasato to differentiate intermediate mesoderm cells into nephron progenitor cells in a medium comprising FGF9 and heparin and the teachings of Takasato for the component concentrations, culturing durations, and marker monitoring as described above; it would have been prima facie obvious to an ordinarily skilled artisan at the time of filing the instant application to modify the method of Ingber to generate the nephron progenitor cells (NPCs) from the intermediate mesoderm cells by culturing the intermediate mesoderm cells in a nephron progenitor induction media comprising 200 ng/mL FGF9 and 1 µg/mL heparin for about 3 days to produce the NPCs, wherein the NPCs express SIX2 and/or CITED1, with a reasonable expectation of success.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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