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 .
Applicant’s submission filed on April 7, 2026 has been entered and considered. Rejections and/or objections not reiterated from the previous action mailed January 7, 2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Election/Restrictions
Applicant’s election of Group 1, claims 1-14, 29, and 36 in the reply filed on December 2, 2025 is acknowledged. It is noted that Applicant has not indicated traversal, therefore the election is being treated as without traverse. Applicant has elected the single specific species of LHX1.
Claims 3-6 and 9-14 were withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 14 and 48 are amended, claims 46-47 and 50 are canceled, and claims 96-98 are newly added. Based on Applicant’s amendment, claim 48 and newly added dependent claims 96-98 have been rejoined.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Applicant has amended claim 48 to more clearly define the claimed method. Claims 1-14, 29, and 36 have been canceled. Claims 99-114 have been newly added.
Newly submitted claims 101-108 and 110-112 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Applicant has previously elected the single specific species of a nephrogenic marker which is LHX1. Accordingly claims 101-108 drawn to various combinations of nephrogenic markers have been withdrawn based on Applicant’s elected species. Similarly, the previous Office Action dated January 7, 2026 examined combinations of LHX1 and RACK-1. Newly added claims 110-112 which recite combinations of LHX1 and other markers which are not RACK-1 have been withdrawn.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 101-108 and 110-112 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 48, 96-100, 109, and 113-114 are examined on the merits.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/US21/59215, filed on November 12, 2021. The instant application claims 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) to U.S. provisional applications 63/113,437, filed on November 13, 2020; 63/214,483, filed on June 24, 2021; and 63/255,704, filed on October 14, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on April 7, 2026 are in compliance with the provisions of 37 CFR 1.97 based on a fee as set forth in 37 CFR 1.17(p) and has been considered by the examiner. The information disclosure statements (IDS) submitted on November 22, 2024; November 11, 2024; and July 24, 2025 are in compliance with the provisions of 37 CFR 1.97 were considered by the examiner.
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Withdrawn Objections to the Specification
Applicant has filed an amended specification which removes hyperlinks and/or browser-executable code and issues related to trade names or marks. Thus, the objection to the specification has been withdrawn.
Withdrawn Claim Rejections - 35 USC § 101
Claims 1-2, 7-8, 29, and 36 were rejected under 35 U.S.C. 101 because the claimed invention is directed to and abstract idea without significantly more. Applicant has canceled claims 1-2, 7-8, 29, and 36 rendering the rejection these claims moot.
Withdrawn Claim Rejections - 35 USC § 103
Claims 1-2, 7-8, 48, 96, and 98 were rejected under 35 U.S.C. 103 as being unpatentable over Presnell et al. (US 2011/0117162 A1, found in IDS dated 7/24/2025, hereafter “Presnell”) and Little et al. (US 2020/0291361 A1, found in IDS dated 7/24/2025, hereafter “Little”). Applicant has canceled claims 1-2 and 7-8 rendering the rejection of these claims moot.
Claims 29 and 36 were rejected under 35 U.S.C. 103 as being unpatentable over Presnell and Little as applied to claim 1, and further in view of Padanilam and Hammerman (1997, Ischemia-induced receptor for activated C kinase (RACK1) expression in rat kidneys. American J. of Phys.-Renal Phys., 272(2), F160-F166). Applicant has canceled claims 29 and 36 rendering the rejection of these claims moot.
New 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 48, 96-100, 109, and 113-114 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.
Dependent claims 96-100, 109, and 113-114 are rejected based on their incorporation of limitations of a rejected base claim while failing to correct the deficiency.
Claim 48, as amended, recites the limitation "a patient" in line 1, “the patient” in line 13, followed by recitation of “a patient” and “the patient” in lines 14-15 related to the source of the enriched heterogeneous renal cell population. As claimed, it is unclear if the recitations of a patient/the patient in lines 14-15 are intended to refer to the same patient as recited in lines 1 and 13, resulting in an autologous enriched heterogeneous renal cell population, a different patient resulting in an allogenic enriched heterogeneous renal cell population, or a combination thus rendering the scope of the claim unclear. Appropriate correction is required.
Claim 113, which depends from claim 48, recites “wherein the enriched heterogeneous renal cell population is sourced from an in vitro culture of cells established from the kidney tissue of the patient” in lines 1-2. Based the multiple recitations of patient in claim 48, recitation of “the patient” is similarly unclear. Appropriate correction is required.
Claim 113 recites the limitation where the separated cells have a “buoyant density of 1.04 m/mL” in line 6, which is a relative term which renders the claim indefinite. The term “buoyant density” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Based on the instant specification, various density gradient media (e.g., glycerol, glucose, OptiPrep, Percoll, Ficoll-Paque) may be used in order to determine the buoyant density of the instantly claimed cells (Pg. 38, 1st para). A skilled artisan would expect the buoyant density of cells to vary based on the density gradient media used. As such, cells having buoyant density of 1.04 g/mL as instantly claimed is relative to the density gradient media used for separation. Additionally, the prior art of Presnell teaches that culture conditions, specifically normoxic/hypoxic conditions, also can affect the buoyant density of cells (See Example 9 and Table 9) as can whether cells being separated are freshly isolated or have been ex vivo cultured (Para. [0389]). As Applicant has not claimed a specific density gradient media, a specific cell population and/or specific culture conditions, the scope of the instant claim is unclear. Appropriate correction is required.
Claim 113 recites the limitation “selecting the separated cells having a buoyant density of 1.04 m/mL” in line 6. Separation by density gradient media results in bands of cell populations that correspond to cells having a range of similar buoyant densities. Therefore, it is unclear base on Applicant’s instant disclosure, how one of ordinary skill in the art would be able to select only those cells having a buoyant density of 1.04 g/mL via use of the claimed density gradient media without also including cells having a buoyant density which is close to 1.04 g/mL, for example cells having a buoyant density of 1.039 g/mL or 1.041 g/mL, thus rendering the scope of the claim unclear. Appropriate correction is required.
Claim 114 is rejected based on its dependency from a rejected claims while failing to correct the deficiencies. Although claim 113 serves to further define the culture conditions which would be expected to have an effect on buoyant density, claim 113 does not clarify the density gradient media. Appropriate correction is required.
New Claim Rejections - 35 USC § 103
This is a new rejection necessitated by Applicant’s amendment. However, this rejection shares substantial similarity to the rejection as previously set forth in the office action dated January 7, 2026. Any aspect of Applicant’s traversal that pertains to the rejection as newly set forth will be provided following the new statement of rejection.
Claims 48, 96, 98-100, and 113-114 are rejected under 35 U.S.C. 103 as being unpatentable over Presnell et al. (US 2011/0117162 A1, found in IDS dated 7/24/2025, hereafter “Presnell”) and Little et al. (US 2020/0291361 A1, found in IDS dated 7/24/2025, hereafter “Little”).
With regard to claims 48, Presnell teaches a method of isolating culturing “admixtures” of renal cell populations (Para. [0011], line 2) which can be used to provide stabilization, improvement, or regeneration of kidney function (Para. [0013], lines 1-3), which is considered to reasonably read on the admixtures having therapeutic potential. Presnell teaches the “admixture” refers to a combination of two or more isolated enriched cell populations derived from an unfractionated heterogeneous cell population (Para. [0205]) and that an enriched cell population refers to a cell population derived from an unfractionated heterogeneous kidney cell population that contains a greater percentage of a specific cell type than in the starting population (Para. [0206]). Additionally, Presnell teaches that the admixture of human renal cells is generated by exposing a cell suspension comprising a non-enriched heterogeneous kidney cell population to hypoxic culture conditions, (Para. [0019], lines 3-4), contacting the cell suspension with a density gradient to separate one or more cell fractions (Para. [0019], lines 12-14), and extracting cell fractions from the density gradient (Para. [0019], line 5) wherein the density gradient is iodixanol (Para. [0242], line 4) and wherein B1 cells having density of less than 1.045g/ml are removed from the admixture (Para. [0012], lines 3-6). Based on the “Preparation of an Enriched Heterogeneous Renal Cell Population” section on Pg. 47 of the instant specification, the admixture of Presnell appears to be prepared by the same steps as instantly disclosed and therefore, Presnell’s teaching of an admixture is considered to reasonably read on the enriched heterogeneous renal cell population as instantly claimed. Further, Presnell teaches that cells of the admixture which can be used for therapeutic purposes are determined to have the presence of various cell-type specific markers (Paras. [0014], [0015], [0016]), including nephrogenic markers such as podocin or nephrin (Para. [0015], line 5).
Presnell does not teach wherein the nephrogenic marker comprises LHX1.
Little teaches kidney organoids and cell populations comprising cells from enzymatic digestion of kidney organoids (Para. [0020]) which have been generated from intermediate mesoderm (IM) cells (Para. [0004], lines 11-12) and which can be used in the treatment of kidney disease (Para. [0020]), which is considered to reasonably read on a renal cell population having therapeutic potential. Little teaches that IM cells develop into the urogenital system including the kidney and exhibit markers which are characteristic of the intermediate mesoderm including LHX1 (Para. [0048]). Further, Little teaches that the kidney organoids comprise cells which express high levels of nephron markers including LHX1 (Para. [0005], lines 5-6 and 8) and that cell population comprising kidney organoids which have been enzymatically digested can be purified to enrich one or more cell types (Para. [0084], lines 19-20) including to form compositions comprising “improved” cells expressing high levels of LHX1 (Para. [0085], lines 3-5). Little teaches that these IM cells can “self-organize” to form kidney organoids (Para. [0054], lines 2-3) and that kidney organoids can comprise architecture similar to native kidney (Para. [0055], lines 9-10). Further, Little teaches that these kidney organoids are more suitable for therapeutic applications (Para. [0008], lines 5-7) including for production of compositions for transplantation (Para. [0010], lines 3-4). Thus, Little provides support for the presence of LHX1 as being an identifiable marker associated with cells having therapeutic potential.
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to identify cells expressing high levels of LHX1 as taught by Little as an indicator of cells having therapeutic potential in the enriched heterogeneous renal cell population as taught by Presnell with a reasonable expectation of success. A skilled artisan would have been motivated to make this identification as Little teaches that cells having high levels of nephrogenic markers including LHX1 have the ability to form kidney organoids having structural features of native kidneys and that these kidney organoids are more suitable for therapeutic applications including transplantation.
In regard to the identifying step, based on the correlation of cells expressing the nephrogenic marker LHX1 being indicative of cells having increased therapeutic potential, one having ordinary skill in the art could have easily identified cells within the enriched heterogeneous renal cell population which express LHX1 as having therapeutic potential based on the combined teachings of Presnell and Little.
Further, Presnell teaches a method of treating kidney disease in a subject in need thereof comprising administration of a composition comprising an “admixture of mammalian renal cells” (Para. [0025], lines 1-4, See also claim 53) which is considered to reasonably read on an enriched heterogeneous renal cell population. As the enriched heterogeneous renal cell population which can be identified by the presence of LHX1 has been made obvious by the combined teachings of Presnell and Little detailed above and incorporated herein, it would be obvious to one having ordinary skill in the art to identify an enriched heterogeneous renal cell population comprising cells expressing LHX1 in the method of Presnell with a reasonable expectation of success. A skilled artisan would be motivated to make this combination as Little teaches that presence of LHX1 is indicative of IM cells which are precursors to kidney development.
With regard to the limitation related to the source of the enriched heterogeneous renal cell population, Presnell teaches the enriched heterogeneous renal cell population can be derived from kidney tissue of a patient or cultured kidney cells, including kidney biopsies and cells cultured from kidney biopsies in vitro (Paras. [0031], [0046], [0062], [0204], [0207], [0219]). Furthermore, in regard to being able to identify LHX1 from this source, Presnell teaches that the retained fractions B3-B4 contain progenitor-like cells which are defined by expression of markers associated with renal development [0500-0506], therefore one of ordinary skill would have had a reasonable expectation of success of identifying the developmentally-associated nephrotic maker LHX1 in the cells of Presnell.
With regard to claim 96, Presnell teaches that the enriched heterogeneous renal cell population may be formulated as a pharmaceutical composition for administration to human beings (Para. [0270], lines 3-4) including in suspension in a pharmaceutically acceptable carrier or excipient (Para. [0269]).
With regard to claim 98, Presnell teaches that the treatment of kidney disease comprises stabilization of kidney function (Para. [0222], lines 5-7).
With regard to newly added claim 99, as detailed above, the combined teachings of Presnell and Little teach an enriched heterogeneous renal cell population having therapeutic potential which can be identified by the presence of cells expressing LHX1. Presnell teaches that an enriched cell population can be identified by having a greater percentage of a specific cell type than the percentage of that cell type in a starting population. Thus, Presnell provides support for determination of the percentage of a specific cell type within a population which a skilled artisan could easily apply to determine the percentage of cells in an enriched heterogeneous cell population which express LHX1 with a reasonable expectation of success. One having ordinary skill in the art would be motivated to make this combination in order to identify the prevalence of LHX1 in a cell population, which the combined teachings of Presnell and Little indicate can be used to identify cells which have therapeutic potential.
With regard to newly added claim 100, firstly, claim 100 recites a wherein clause directed to the percentage of LHX1 expressing cells. MPEP 2111.04 (II) indicates that he broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met.
For example, assume a method claim requires step A if a first condition happens and step B if a second condition happens. If the claimed invention may be practiced without either the first or second condition happening, then neither step A or B is required by the broadest reasonable interpretation of the claim. If the claimed invention requires the first condition to occur, then the broadest reasonable interpretation of the claim requires step A. If the claimed invention requires both the first and second conditions to occur, then the broadest reasonable interpretation of the claim requires both steps A and B.
The broadest reasonable interpretation of a system (or apparatus or product) claim having structure that performs a function, which only needs to occur if a condition precedent is met, requires structure for performing the function should the condition occur. The system claim interpretation differs from a method claim interpretation because the claimed structure must be present in the system regardless of whether the condition is met and the function is actually performed.
See Ex parte Schulhauser, Appeal 2013-007847 (PTAB April 28, 2016) for an analysis of contingent claim limitations in the context of both method claims and system claims. In Schulhauser, both method claims and system claims recited the same contingent step. When analyzing the claimed method as a whole, the PTAB determined that giving the claim its broadest reasonable interpretation, "[i]f the condition for performing a contingent step is not satisfied, the performance recited by the step need not be carried out in order for the claimed method to be performed" (quotation omitted). Schulhauser at 10. When analyzing the claimed system as a whole, the PTAB determined that "[t]he broadest reasonable interpretation of a system claim having structure that performs a function, which only needs to occur if a condition precedent is met, still requires structure for performing the function should the condition occur." Schulhauser at 14. Therefore "[t]he Examiner did not need to present evidence of the obviousness of the [ ] method steps of claim 1 that are not required to be performed under a broadest reasonable interpretation of the claim (e.g., instances in which the electrocardiac signal data is not within the threshold electrocardiac criteria such that the condition precedent for the determining step and the remaining steps of claim 1 has not been met);" however to render the claimed system obvious, the prior art must teach the structure that performs the function of the contingent step along with the other recited claim limitations. Schulhauser at 9, 14.
Secondly, the combined teachings of Presnell and Little teach an enriched heterogeneous renal cell population having therapeutic potential which can be identified by the presence of cells expressing LHX1 and Presnell provides support for determination of the percentage of a specific cell type which a skilled artisan could easily apply to cells expressing LHX1.
The combination of Presnell and Little does not directly teach a percentage of LHX1-expressing cells which is greater than about 8% of the enriched heterogenous renal cell population.
However, Little teaches that cells identified as committed nephron progenitors, which express LHX1, are the most abundant cell type (430 cells) in the population of cells of kidney organoids (1673 cells) (See Example 10 and Fig. 3A), comprising approximately 25% of the total population. Thus, it would have been obvious to one having ordinary skill in the art to apply a starting point for identifying therapeutic potential when about 25% of cells are LHX1 positive as taught by Little to the enriched heterogenous renal cell population of Presnell with a reasonable expectation of success. A skilled artisan would have been motivated to make this combination as Little teaches LHX1-expressing kidney organoids with improved therapeutic potential and that approximately 25% of cells in these kidney organoids express LHX1.
Independently, it appears that the cell population as taught by Presnell would inherently comprise about 8-57% of cells (i.e., greater than about 8%) which express LHX1. The “admixture” as taught by Presnell and the instantly claimed enriched heterogeneous renal cell population appear to be prepared by the same process and thus appear to be the same product. Based on the instant specification, the enriched heterogeneous renal cell population (which is produced by the same method as Presnell as detailed above) was tested for expression of nephrogenic markers (See Example 2) in order to determine the expression level of LHX1 across enriched heterogeneous renal cell populations resulting in the determination that the range of percentage of cells expressing LHX1 in enriched heterogeneous renal cell populations was between 8.5% and 57.1% (See Tables 4 and 5). Although Presnell had good reason to measure LHX1 levels as a correlation of therapeutic potential (see above), they are silent as to the characterization of the expression of LHX1 in their cell population. However, since the cell population as taught by Presnell appears to be the same cell population as instantly claimed, one having ordinary skill in the art could reasonably expect that greater than about 8% of the cells as taught by Presnell would inherently express LHX1 if they were to be assayed for LHX1 expression. Thus, the specific percentage of cells which express LHX1 in an enriched renal cell population appears to be inherent to the population when produced by the method of Presnell and as instantly claimed, absent evidence to the contrary (See MPEP 2112(I)).
With regard to newly added claim 113, as detailed above, Presnell teaches the enriched heterogeneous renal cell population can be derived from kidney tissue of a patient or cultured kidney cells, including kidney biopsies and cells cultured from kidney tissue in vitro (Paras. [0031], [0046], [0062], [0204], [0207], [0219]). Presnell teaches an example embodiment (see Example 8) where cells sourced from kidney tissue (Para. [0381]) are plated and cultured (Para. [0386]) which is considered to reasonable read on passaging of cells, and then collected and subjected to a density gradient in order to separate specific cell populations (Para. [0388]). Presnell teaches that the desired population of B2 bioactive renal cells derived from cultured cells has a density between 1.045 g/L and 1.052 to 1.063 g/mL based on species and the desired population of B4 bioactive renal cells derived from cultured cells has a density between 1.063 g/L-1.073 and 1.091 g/mL based on species (See Table 8). Therefore, a skilled artisan would have recognized, based on the teachings of Presnell, that selecting separated cells having a buoyant density of 1.04 g/mL and removing them would result in enriched bioactive cell population comprising the desired populations of bioactive renal cells which have densities greater than 1.04 g/mL. (See also Example 10, in particular Para. [0401]).
With regard to newly added claim 114, Presnell teaches that the passaged cells sources from in vitro culture of kidney tissue are placed in a 2% oxygen environment, which is considered to reasonably read on hypoxic conditions, (Para. [0386], [0388], see also Example 10 and Para. [0401]) and that the distribution of cells into the desired populations of bioactive renal cells can be “enhanced” by exposure to hypoxic conditions (Para. {0389]).
Response to Arguments
Applicant's arguments filed April 7, 2026 have been fully considered but they are not persuasive.
Applicant traverses the rejection of claim 48 over Presnell and Little on Pg. 16 by asserting that since newly amended claim 48 recites that the enriched heterogeneous renal cell population is sourced from a kidney biopsy of a patient or an in vitro culture of cells established from a kidney tissue of the patient, Presnell in view of Little fails to teach or suggest the newly added limitation of claim 48. Applicant asserts on Pg. 17 that Little discloses expression of LHX1 in human pluripotent stem cells or human embryonic stem cells but does not teach that the cells are sourced from a kidney biopsy or a patient or an in vitro culture of cells established from kidney tissue of the patient and therefore that the combination of Presnell and Little does not disclose determining LHX1 expression in the instantly claimed cells.
Applicant’s arguments have been fully considered but are not persuasive.
As detailed in the new rejections under 35 U.S.C. 103, Presnell teaches that the enriched heterogeneous cell population can be sourced from a kidney biopsy of a patient or an in vitro cell culture derived from kidney tissue of a patient. Furthermore, in regard to being able to identify LHX1 from this source, Presnell teaches that the retained fractions B3-B4 contain progenitor-like cells which are defined by expression of markers associated with renal development [0500-0506]. Additionally, Presnell teaches that the B3 and B4 fragments exhibit therapeutic potential (See Example 14 and Table 13 and Example 15 and Table 15) and, therefore, a skilled artisan could have easily envisioned further exploration of renal developmental markers. As the teachings of Little are drawn to examination of developmental markers in renal tissue, one of ordinary skill would have recognized the nexus between the teachings of Presnell and Little as it relates to renal progenitor cells and developmental markers and have had a reasonable expectation of success of identifying the developmentally-associated nephrotic maker LHX1 as taught by Little in the cells of Presnell. Thus, the limitations regarding the source of the enriched heterogeneous renal cell population are taught by the prior art of Presnell and the instantly claimed method of treating kidney disease comprising identification of a cell population having therapeutic potential based on expression of LHX1 is rendered obvious by the combination of Presnell and Little.
Claim 97 is rejected under 35 U.S.C. 103 as being unpatentable over Presnell and Little as applied to claim 48 above, and further in view of Stenvinkel et al. (2016, Implantation of autologous selected renal cells in diabetic chronic kidney disease stages 3 and 4 - clinical experience of a “first in human” study. Kidney Intl Rep, 1(3), 105-113, found in IDS dated 11/22/2024, and Supplementary material, attached, hereafter “Stenvinkel”).
With regard to claim 97, as detailed above the combined teachings of Presnell and Little teach a method of treating kidney disease comprising use of an enriched heterogeneous renal cell population identified as having therapeutic potential by the expression of LHX1. Presnell teaches that administration of the enriched heterogeneous renal cell population can be via intra-renal (e.g., parenchymal) injection (Para. [0276], lines 1-5) including percutaneous injection (Para. [0276], line 9).
While Presnell teaches exemplary embodiments wherein the injection was administered into the corticomedullary region of the kidney (Para. [0322]), Presnell does not teach administration into the renal cortex.
Stenvinkel teaches administration of selected renal cells (SRCs) to patients having chronic kidney disease (Abstract). The SRCs as taught by Stenvinkel appear to have been prepared by similar methods comprising starting material from kidney biopsies, cultured under hypoxic conditions, and subjected to a iodixanol gradient (Supplementary material, Preparation of selected renal cells) and the instant specification repeatedly refers to the enriched heterogeneous renal cell population as SRCs (see Table 7; Pg. 63, lines 11, 15, 18, 26, 31) , thus the SRCs as taught by Stenvinkel are considered to reasonably read on an enriched heterogeneous renal cell population as instantly claimed. Stenvinkel teaches that administration of the enriched heterogeneous renal cell population (i.e., SRCs) resulted in postoperative complications and that future trials comprising administration of an enriched heterogeneous renal cell population (i.e., SRCs) should use safer delivery methods such as percutaneous delivery to the renal cortex (Discussion, 1st para.).
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to apply percutaneous delivery of an enriched heterogeneous renal cell population into the renal cortex to the method of treatment of kidney disease comprising percutaneous injection of enriched heterogeneous renal cell population in the corticomedullary region as taught by Presnell with a reasonable expectation of success. A skilled artisan would have been motivated to make this combination as Stenvinkel teaches that percutaneous administration to the renal cortex is a safer method of delivery of an enriched heterogeneous renal cell population and that existing methods resulted in postoperative complications, which one having ordinary skill in the art would recognize as important for treatment in human subjects.
Response to Arguments
Applicant's arguments filed April 7, 2026 have been fully considered but they are not persuasive.
Applicant traverses on Pg. 18 the rejection of claim 97 over Presnell, Little, and Stenvinkel based on its dependency from claim 48 and Applicant’s traversal that the combination of Presnell and Little do not teach that the enriched heterogeneous renal cell population is sourced from a kidney biopsy of a patient or an in vivo culture of cells established from a kidney tissue of the patient. Applicant asserts that Stenvinkel fails to cure the alleged deficiencies of Presnell and Little.
Applicant’s arguments have been fully considered but are not persuasive.
As stated in the response to arguments above regarding claim 48 and in the new rejections under 35 U.S.C. 103, Presnell teaches that the enriched heterogeneous cell population can be sourced from a kidney biopsy of a patient or an in vitro cells culture derived from kidney tissue of a patient.
Claim 109 is rejected under 35 U.S.C. 103 as being unpatentable over Presnell and Little as applied to claim 48 above, and further in view of Padanilam and Hammerman (1997, Ischemia-induced receptor for activated C kinase (RACK1) expression in rat kidneys. American J. of Phys.-Renal Phys., 272(2), F160-F166).
With regard to claim 109, as detailed above in claim 48, the combined teachings of Presnell and Little teach an enriched heterogeneous renal cell population having therapeutic potential which can be identified by the presence of cells expressing LHX1.
While Presnell does teach that cells of an enriched cell population which can be used for therapeutic purposes can be identified based on presence of various markers (Paras. [0014], [0015], [0016]), Presnell does not teach expression of RACK-1.
Padanilam and Hammerman teach that recovery from acute ischemic renal failure requires regeneration of kidney cells specifically, proliferation of dedifferentiated renal cells, migration, and redifferentiation of cells in order to repair damaged nephron tissue (Pg. F160, left col., 1st para. and Pg. Additionally, Padanilam and Hammerman teach that that RACK-1 expression is upregulated in the kidneys of rats following ischemic injury (Abstract) and is localized in cells that are regenerating and remains upregulated for the duration of the time that regeneration of tissue is occurring (Pg. F165, right col., last para.) Further, Padanilam and Hammerman teach that RACK-1 expression plays a role in regulation of cellular proliferation in the regeneration process in kidney cells after injury (Abstract).
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention to combine Padanilam and Hammerman’s teaching that RACK-1 expression is associated with cellular proliferation and regeneration in kidneys after injury with the combination of Presnell and Little which teach selection of an enriched heterogeneous renal cell population having therapeutic potential based on expression of LHX1 with a reasonable expectation of success. Since Padanilam and Hammerman teach RACK-1 is an indicator proliferative ability in kidney cells and the combination of Presnell and Little teach that LHX1 is an indicator of an enriched heterogeneous renal cell population having therapeutic potential, a skilled artisan would have been motivated to make this combination in order to select the enriched heterogeneous renal cell population which is likely to have the best proliferative ability in order to maximize therapeutic results.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 48, 96-97, 99-100, 109, 113 and 114 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 34 of copending Application No. 19/227,186 (reference application) in view of the combined teachings of Presnell, Little, Stenvinkel and Padanilam and Hammerman. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the method of treating kidney disease in a patient in need thereof by administration of a therapeutically effective amount of an enriched heterogeneous cell population (also referred to as SRCs), expressing LHX1 and further expressing RACK-1 as instantly claimed makes obvious the method of treating kidney disease comprising injecting into the renal cortex a therapeutically effective amount of a composition comprising and SRC population as claimed in reference application ‘186. The difference between the instant claims and the reference claims lies in the fact that the instant application claims are more specific to the type of enriched heterogeneous renal cells (i.e., SRCs) which are to be administered.
With regard to claims 48 and 96-97, 99-100, 109, 113 and 114 as detailed above and incorporated herein, the combined teachings of Presnell, Little, and Stenvinkel teach a method of treatment of chronic kidney disease in a patient comprising administration of a therapeutically effective amount of an enriched heterogeneous cell population identified by the presence of the marker LHX1. Padanilam and Hammerman further teach that RACK-1 expression is associated with cellular proliferation and regeneration in kidneys after injury and make obvious the combination of LHX1 and RACK-1 as expression markers for renal cells having therapeutic potential. Stenvinkel teaches administration of selected renal cells (SRCs) to patients having chronic kidney disease (Abstract). The SRCs as taught by Stenvinkel appear to have been prepared by similar methods to those as instantly claimed comprising starting material from kidney biopsies, cultured under hypoxic conditions, and subjected to a iodixanol gradient (Supplementary material, Preparation of selected renal cells) and the instant specification repeatedly refers to the enriched heterogeneous renal cell population as SRCs (see Table 7; Pg. 63, lines 11, 15, 18, 26, 31), thus the SRCs as taught by Stenvinkel are considered to reasonably read on an enriched heterogeneous renal cell population as instantly claimed. Stenvinkel teaches that future trials comprising administration of an enriched heterogeneous renal cell population (i.e., SRCs) should use delivery methods such as percutaneous delivery to the renal cortex (Discussion, 1st para.), which is considered to reasonably read on a minimally invasive procedure. Further, Presnell teaches that the enriched heterogeneous renal cell population may be formulated as a pharmaceutical composition for administration to human beings (Para. [0270], lines 3-4) including in suspension in a pharmaceutically acceptable carrier or excipient (Para. [0269]). Thus, based on the teachings of Presnell, Little, Stenvinkel, and Padanilam and Hammerman SRCs identified as expressing LHX1 and further expressing RACK-1 would be an obvious type of SRC to administer in a method of treating chronic kidney disease. Since the instant application claims are obvious over the reference application ‘186 claims 1-2 and 34, said claims are not patentably distinct.
Response to Arguments
Applicant's arguments filed April 7, 2026 have been fully considered but they are not persuasive.
Applicant traverses the provisional non-statutory double patenting rejection in view of lack of allowable subject matter and asserts that an appropriate response will be provided in the event of indication of allowable subject matter (Pg. 19, last para.).
Applicant’s traversal is acknowledged.
Based on Applicant’s amended claims, the provisional non-statutory double patenting rejection has been updated and is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIN V PAULUS whose telephone number is (571)272-6301. The examiner can normally be reached Mon-Fri 8 AM-5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Doug Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIN V PAULUS/Examiner, Art Unit 1631
/ARTHUR S LEONARD/Examiner, Art Unit 1631
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