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 with traverse of Group I in the reply filed on 07/07/2026 is acknowledged. The traversal is on the ground(s) that claims 13 and 16 have been amended to depend directly from claim 1, therefore, claims 13-20 each require all limitations of claim 1 and are directed to specific embodiments of the elected invention. The argument has been considered but is not found persuasive. This is because the instant application is a national stage application filed under 35 U.S.C 371. Accordingly, the applicable standard for restriction practices is the requirement of unity of invention. It should be noted that Group I, II, and III share a special technical feature represented by the use of renal interstitial progenitor cells produced according to claim 1. However, this common special technical feature is not a special technical feature as it does not make a contribution over the prior art, because the generation of renal interstitial progenitor cells were known in the prior art ( See claim 1 rejection below). Therefore, the requirement is still deemed proper and is therefore made FINAL.
Claims 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Applicant timely traversed the restriction (election) requirement in the reply filed on 7/07/2026.
Claims Status
Claims 13 and 16 are amended.
Claims 1-20 are pending.
Claims 13-20 are withdrawn.
Claims 1-12 are under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or
under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. However, Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is
also disclosed in the prior application (the parent or original nonprovisional application or
provisional application). The disclosure of the invention in the parent application and in the later-
filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the
first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco
Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir.
1994).
It is noted that the disclosure of the prior-filed applications, Application No. 63232102,
and 63362846, does not provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for claims 1-12 as none of the two claimed priority applications discloses the claimed method starting with culturing of HOXC10-positive cells. The claimed priorities are thus not valid for the subject-matter of claims 1-12 on file. Therefore, the priority date for the instant claims is the filing date of the present application, i.e. 10/08/2022.
Information Disclosure Statement
The information disclosure statement (IDS) was filed before the
mailing date of the non-final first action on the merits. The submission is in compliance with the
provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being
considered by the examiner.
Allowable Subject Matter
Claim 3 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims Status
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 1-6 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.
Claim 1 recites a method of producing renal interstitial progenitor cells (IPC) comprising culturing “HOXC10-positive” cells in a medium comprising a GSK3B inhibitor, a SHH signal activator, and a TGFB inhibitor to induce renal interstitial progenitor cells. It should be noted that the claim when given its broadest reasonable interpretation consistent with the specification, encompasses methods employing HOXC10-positive cells generally, without requiring the HOXC10-positive cells be obtained by differentiation from pluripotent stem cells, and without requiring that the cells constitute HOXC10-positive posterior primitive streak cells , and without requiring the particular differentiation process as described in [0105] of the instant specification for generating those cells. The specification, however, does not demonstrate possession of the full breadth of this claimed genus.
The specification defines the invention as a method of differentiating HOXC10-positive cells into renal interstitial progenitor cells. The specification also includes the detailed method concerning the generation of the starting HOXC10-positive cells via a particular differentiation pathway from pluripotent stem cells. Specifically, the specification describes a sequence of differentiation steps comprising: (i) culturing pluripotent stem cells in a medium comprising
bFGF , BMP4, a GSK-3β inhibitor, and retinoic acid or a derivative thereof; (ii) culturing the cells obtained in Step (i), in a medium comprising bFGF, a GSK-3β inhibitor, and BMP7; (iii) culturing the cells obtained in Step (ii) in a medium comprising a GSK-3β inhibitor and a TGFβ inhibitor; and (iv) culturing the cells obtained in Step (iii), in a medium comprising bFGF, a GSK-3β inhibitor, activin, and a ROCK inhibitor. ([0074]). The specification states that step (iv) induces HOXC10-positive posterior primitive streak cells, characterized as metanephric-lineage primitive streak cells. (See [0093]). The working examples likewise uses human pluripotent stem cells and the aforementioned differentiation sequences to generate HOXC10 and CITED1-positive posterior primitive streak cells. Those cells are subsequently subjected to renal interstitial progenitor cells differentiation condition. The specification reports the induction of FOXD1 positive cells and further reports increased induction efficiency upon addition of SHH agonist, and in certain experiments, IL-1β.
In other words, the instant specification provides substantial detail concerning a particular starting cell population HOXC10-positive posterior primitive streak cells generated through differentiation from pluripotent stem cells and the particular differentiation condition used to generate renal interstitial progenitor cells from that population. Claim 1, however, is not limited to that disclosed population. Instead, the claim encompasses any HOXC10-positive cells obtained by routes other than the disclosed pluripotent stem cell differentiation pathway, and cell populations other than the specifically described posterior primitive streak population.
On the other hand, prior art by Mouilleau et al ( Development, 2021) describes human pluripotent stem cell derived axial progenitor cells in which HOX activation produces distinct rostro-caudal identities, including HOXC10-positive population associated with specification of motor-neuron subtypes. Thus, HOXC10 positivity was not limited to renal stromal or renal interstitial cell identity, rather was associated with distinct developmental cell populations. Therefore, the instant specification does not adequately demonstrate possession of the full genus of HOXC10-positive cells encompassed by claim 1. It is submitted that the specification provides detailed support for HOXC10-positive posterior primitive streak cells generated from pluripotent stem cells, but does not provide corresponding disclosure demonstrating possession of every other HOXC10-positive cell population encompassed by claim 1 as suitable starting material for producing renal interstitial progenitor cells under the claimed conditions. Accordingly, claim 1 is rejected under 35 U.S.C 112(a).
As per the MPEP (2163 (I)). “ To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
As per the MPEP (2163 (V)).” While there is a presumption that an adequate written description of the claimed invention is present in the specification as filed. In re Wertheim, 541 F.2d 257, 262, 191 USPQ 90, 96 (CCPA 1976), a question as to whether a specification provides an adequate written description may arise in the context of an original claim. An original claim may lack written description support when…(2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc).
Claims 2-6 depend from claim 1 and include further limitation which do not cure the lack of written-description for the full breadth of the starting-cell limitation inherited from claim 1. Accordingly, claims 2-6 are likewise rejected under 35 U.S.C 112(a).
Applicant attention is directed to the exiting narrower disclosure, in particular claims 7-8 reciting the source of the HOXC-10 cells (i.e. pluripotent stem cells), and the four-step differentiation process. Applicant is invited to amend the independent claims, if appropriate, to bring the scope of the claims into conformity with the subject matter adequately described in instant specification by incorporating the limitation of claims 7-8 in the subject matter of the independent claim 1.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1,4-12 are rejected under 35 U.S.C. 103 as being unpatentable over Ikeya et al ( WO 2020250913 A1), in view of Sueta et al ( US 2020/0248148 A1), Patterson et al ( Developmental Dynamic, 2004) , Yallowitz et al ( PLOS ONE, 2011), and Sheybani-Deloui et al ( Journal of American Society of Nephrology, 2018). WO 2020250913 A1 is in the
Japanese language. A machine translation is provided herewith. Citations are made to the machine translation.
Regarding claims 1, 4, and 6, Ikey at al teach a method for producing renal interstitial/stromal cells. Specifically, Ikey et al teach a differentiation pathway involving neuronal crest cells and renal stromal progenitor cells. The method of Ikey et al involves culturing pluripotent stem cells in a medium containing GSK3B inhibitor, TGFB inhibitor and retinoic acid derivative to direct their differentiation into neural crest cells. Followed by differentiation of the neural crest cells toward renal stromal precursor cells including renal interstitial progenitor cells. ( See claims 1-9). Accordingly, Ikey et al teach the use of TGFB inhibitor, GSK3B inhibitor and retinoic acid in a differentiation pathway directed toward renal stromal/interstitial progenitor cells.
In addition, Sueta et al disclose a method of producing renal progenitor cells comprising inducing differentiation from intermediate mesodermal cell and pluripotent stem cells into renal progenitor cells. [0014]. Specifically, Sueta et al’s method involves culturing intermediate mesodermal cells in a medium containing a GSK3B inhibitor and FGF 9, to induce renal progenitor cells from intermediate mesodermal cells. [0016]. Sueta et al also identifies CHIR99021 as a preferred GSK3B inhibitor. [0016]. Most importantly, Sueta et al disclose a preceding differentiation step in which cells are cultured in a medium containing FGF2, a GSK3B inhibitor, BMP7, and TGFB inhibitor. [0024, specifically the corresponding step (iii)]. Sueta et al also identifies A83-01 as a preferred TGFB inhibitor. [0077]. Sueta et al further teach that the differentiation sequence proceeds toward a late posterior intermediate mesoderm, characterized by OSR1,HOX11, and WT1 and that the resulting intermediate-mesoderm cells can subsequently be cultured in a medium containing GSK3B inhibitor and FGF9 to induce renal progenitor cells. ( See the corresponding step (v) and the renal progenitor induction step in [0087]). Accordingly, Sueta et al confirms that the modulation of the developmental signaling pathways, including a GSK3B inhibition and TGFB inhibition in the production of renal progenitor cells were known before the effective filing date of the claimed invention.
However, neither Ikey nor Sueta et al expressly teach the starting HOXC10-positive cells, nor the use of SHH signal activator in the renal progenitor differentiation step.
Patterson et al supplement Ikey and Sueta et al by teaching that HOXC10 expression is restricted to the mesenchyme during kidney development, and provides E13.5 in situ hybridization showing mesenchyme-restricted HOXC10 expression. ( See Fig.1). Accordingly, Patterson et al establishes that HOXC10-positive renal mesenchymal cells were known before the effective filing date.
Yallowitz et al further teach that HOX10 genes have a functional role in the development and integration of cortical stromal cells. Specifically, Yallowitz et al report that HOX10 genes are expressed in the cortical stromal cell population surrounding the developing kidney and that although Foxd1 positive stromal cells initiate normally in HOX10 mutants, those cells fail to fully integrate into the developing kidney. Yallowitz concludes that HOX10 has a critical function promoting integration of the cortical stromal lineage. ( See 2nd column – 2nd paragraph-on page 7). Thus, establishing a relationship between HOX10 expression and renal stromal/interstitial development. Accordingly, the combined teachings of Patterson and Yallowtiz would have identified HOXC10-positive renal mesenchymal cells as belonging to a HOX10 associated renal stromal developmental context, and would have provided one with ordinary skill in the art with a reason to consider HOX10/HOXC10-positive renal mesenchymal cells when directing the differentiation toward renal stromal/interstitial population.
Sheybani-Deloui et al further supplement Ikey and Sueta et al by expressly stating that the majority of Foxd1 positive stromal progenitor cells (i.e. interstitial progenitor cells) originate from the Osr1-positive posterior intermediate mesoderm, and that stromal-lineage specification occurs between E9.5 and E11. Sheybani-Deloui et al further report an evidence that SHH signaling plays a role in stromal-cell specification from precursor cells. Specifically, Sheybani-Deloui et al report that activation of SHH signaling in renal precursor cells resulted in an ectopic population of stromal cells. Lineage tracing experiments demonstrated that the ectopic stromal cells were direct descendent of intermediate-mesoderm-derived renal progenitor cells. Sheybani-Deloui show that Ptch2-positive cells resulting from SHH activation expressed genes characteristic of stromal progenitor cells. Accordingly, Sheybani-Deloui teach that SHH signaling is a developmental signal capable of affecting the specification of renal stromal lineage from intermediate-mesoderm-derived renal progenitor cells. ( See abstract). As such, Sheybani-Deloui would have provided an ordinary skill in the art with a reason to consider SHH pathway activation when directing intermediate-mesoderm-derived renal progenitor cells toward a stromal/interstitial lineage. This teaching is relevant to the claimed production of renal interstitial progenitor cells because the reference associates SHH signaling with the specification of stromal progenitor cells arising from intermediate-mesoderm renal progenitor cells.
Taken together, Ikey at al teach a method of differentiating neural crest stem cells into renal stromal/interstitial progenitor by modulating the GSK3B and TGFB pathways. Sueta et al teach a renal differentiation system using GSK3B and TGFB pathway modulation, and show that modulation of GSK3B and TGFB signaling can direct cells through intermediate mesoderm toward renal progenitor population. Pattereson and Yallowitz establish that Hoxc10 is expressed in the renal mesenchymal compartment and cortical stromal populations. Sheybani-Deloui provide a renal-developmental reason to manipulate SHH signaling when seeking stromal cell specification, specifically demonstrating that renal progenitor derived from intermediate mesoderm respond to SHH activation and that the activation of SHH affects the stromal cell fate. Accordingly, an ordinary skill in the art would have had a reasonable expectation that applying these known pathways manipulation to a renal differentiation system would affect differentiation of the renal stromal/interstitial population.
Regarding claim 5, Ikey et al expressly teach that its differentiation method maybe performed using suspension culture. [0042].
Regarding claims 7-8, following the discussion of claim 1 above, the combined teachings of Ikey and Sueta in view of the cited prior arts render obvious claim 1. The differentiation method of Ikey et al begins with pluripotent stem cells and proceeds through differentiation toward renal interstitial progenitor cell. (claims 1-9). Sueta et al’s method likewise start with pluripotent stem cells and proceeds toward renal progenitor cells. This reads on claim 7. Sueta et al further describe sequential differentiation of pluripotent stem cells through renal developmental stages to produce renal progenitor cells. Specifically, Sueta et al teach
step of culturing pluripotent stem cells in a medium containing FGF2, BMP 4, a GSK-3B inhibitor, and retinoic acid or a derivative;
culturing cells obtained in Step (i) in a medium containing FGF2, a GSK-3B inhibitor, and BMP7;
a step of culturing cells obtained in Step (ii) in a medium containing FGF2, a GSK-3B inhibitor, BMP7, and a TGFB inhibitor; and
a step of culturing cells obtained in Step (iii) in a medium containing FGF2, a GSK-3B inhibitor, BMP7, activin, and a ROCK inhibitor; ( See [0017-0020]).
Sueta et al, therefore teach substantially the same sequential signaling manipulation recited in claim 8 for directing the differentiation of pluripotent stem cells toward a renal progenitor cells.
Regarding claim 9, following the discussion of claims 1 and 7 above, Ikey et al teach that induced pluripotent stem cells can be used as the starting population for the production of renal interstitial progenitor cells. ( [0006] in Ikey disclosure). Sueta et al, likewise, expressly teach the use of induced pluripotent stem cells as the starting population for differentiation into renal progenitor cells. ( See claim 11 in Sueta disclosure). Thus, the selection of iPSCs as the starting population would have been expressly taught by Ikey and Sueta et al and would not have imparted a patentable weight to the method of claim 7.
Regarding claim 10, recites a product-by-process limitation, because the process by which the renal interstitial progenitor cells is produced, dose not distinguish the claimed cells from prior art cells where the prior art cells are the same or substantially the same product. Thus. the claimed cells would have been obvious in view of the combined teachings of the cited prior art. It should be noted that product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Consequently, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113.
Regarding claim 11-12, following the discussion of claim 1, Sueta et al further disclose a pharmaceutical composition containing the renal progenitor cells and therapeutic use of the renal progenitor cells for kidney disease.[0097]. Ikey et al similarly identify renal stromal/interstitial cells as useful cell population for renal research and organoids construction. [0068]. Therefore, it would have been obvious to formulate the renal interstitial cells produced by the combined teachings of the cited prior art in a pharmaceutical composition for therapeutic use. Sueta et al further describe the cells being produced to be equivalent to nephron progenitor cells, therefore, the composition produced by the combined teachings of the cited prior art would also include nephron progenitor cells, this reads on claim 12 .( see [0036])
Claim(s) 2 is rejected under 35 U.S.C. 103 as being unpatentable over Ikeya et al, in view of Sueta et al, Patterson et al, Yallowitz et al , and Sheybani-Deloui et al, as applied to claims 1,4-12 above, and further in view of Lemos et al .
Regarding claim 2, following the discussion of claim 1 above, the combined teachings of the applied prior arts render obvious claim 1. Claim 2 requires the medium further contains IL1b .
Lemos et al supplement the cited prior art by teaching the use of IL-1b in a human renal cell culture system. Specifically, Lemos et al teach a method of generating kidney organoids. The method involves directing the differentiation of human pluripotent stem cells and subsequently exposing the kidney organoids to IL-1b. Lemos et al show that IL-1b stimulation increases the proliferation of PDGFR-positive renal stromal cells and activated the renal stromal cell population. ( See section “ Generation of Human Kidney Organoids and IL-1b Stimulation” on page 1692). Thus, Lemos et al establishes that, before the effective filing date of the claimed invention, that IL-1b was a known signaling factor that could be included in a culture medium containing renal stromal cells and used to modulate the proliferation and activation of such cells. As such, it would have been prima facie obvious to one with ordinary skill in the art at the time the invention was filed to further modify the renal stromal/interstitial differentiation method of claim 1 by including IL1b in the culture medium, as taught by Lemos et al, in order to promote the proliferation and activation of the renal stromal cell population. In other words, claim 2 is Combining prior art elements according to known methods to yield predictable results. See MPEP 2143 (I)(A).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FATIMAH KHALAF MATALKAH whose telephone number is (703)756-5652. The examiner can normally be reached Monday-Friday,7:30 am-4:30 pm EST.
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/FATIMAH KHALAF MATALKAH/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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