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 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Claims 3-6 and 9-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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, to 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).
Claims 1-2, 7-8, 29, 36, 48, and 96-98 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 November 22, 2024; November 11, 2024; and July 24, 2025 are in compliance with the provisions of 37 CFR 1.97 and are being 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.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on Pg. 56, Pg. 65, Pg. 66. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term Viaspan, HypoThermosol-FRS in Table 1, HyperStacks in line 16 of Pg. 45, Cellometer in line 18 of Pg. 46 and line 23 of Pg. 47, Optiprep in line 15 of Pg. 54 which is a trade name or a mark used in commerce, has been noted in this application. This is not intended to be an exhaustive list. It is recommended that Applicant thoroughly review the specification for other trade names or marks. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
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.
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.
Claims 1-2, 7-8, 29, and 36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to and abstract idea without significantly more.
MPEP 2106.04 states:
In addition to the terms "laws of nature," "natural phenomena," and "abstract ideas," judicially recognized exceptions have been described using various other terms, including "physical phenomena," "products of nature," "scientific principles," "systems that depend on human intelligence alone," "disembodied concepts," "mental processes," and "disembodied mathematical algorithms and formulas." It should be noted that there are no bright lines between the types of exceptions, and that many of the concepts identified by the courts as exceptions can fall under several exceptions. For example, mathematical formulas are considered to be a judicial exception as they express a scientific truth, but have been labelled by the courts as both abstract ideas and laws of nature. Likewise, "products of nature" are considered to be an exception because they tie up the use of naturally occurring things, but have been labelled as both laws of nature and natural phenomena. Thus, it is sufficient for this analysis for the examiner to identify that the claimed concept (the specific claim limitation(s) that the examiner believes may recite an exception) aligns with at least one judicial exception.
Claim 1 recites a method of identifying an enriches heterogeneous renal cell population has having therapeutic potential and claims 2, 7, and 29 depend from claim 1, claim 8 depends from claim 2, and claim 36 depends from claim 29. Claims 1-2, 7-8, 29, and 36 are drawn to the statutory category of a process and are eligible under Step 1.
Claim 1 recites wherein the method comprises “determining whether cells of the enriched heterogeneous renal cell population express at least one nephrogenic marker and identifying the enriched heterogeneous renal cell population as having therapeutic potential if cells of the enriched heterogeneous renal cell population are determined to express at least one nephrogenic marker.” The broadest reasonable interpretation of “determining” and “identifying” includes evaluation and judgement. Thus, claim 1 recites a concept that falls into the mental processes group of abstract ideas.
Claim 2, which depends from claim 1, recites “wherein the step of determining comprises determining the percentage of cells of the enriched heterogeneous renal cell population that express at least one nephrogenic marker”. Thus, the determining step is performed by generating a percentage of the population of cells and therefore recites a concept that falls into the mathematical concepts group of abstract ideas.
Claims 7 and 8, which depend from claims 1 and 2 respectively, recite “wherein the at least one nephrogenic marker comprises LHX1” and wherein “the enriched heterogeneous renal cell population is identified as having therapeutic potential if about 8% to about 58% of the cells…are determined to express LHX1”. Thus, claims 7 and 8 recite limitations which include evaluation and judgement and recite concepts that fall into the mental processes group of abstract ideas.
Claim 29, which depends from claim 1, recites additional limitations wherein the method of claim 1 further comprises “determining whether the cells of the enriched heterogeneous renal cell population express RACK-1 and identifying the enriched heterogeneous renal cell population as having a therapeutic potential if cells of the enriched heterogeneous renal cell population are further determined to express RACK-1”. Similar to claim 1, the broadest reasonable interpretation of “determining” and “identifying” includes evaluation and judgement. Thus, claim 29 recites a concept that falls into the mental processes group of abstract ideas.
Claim 36, which depends from claim 29, recites wherein “the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that at least about 85% of cells…express RACK-1”. Similar to claims 2 and 8, this limitation involves generating a percentage of the population of cells and subsequent evaluation and judgement and therefore recites concepts that fall into the mathematical concepts and mental processes groups of abstract ideas.
Thus, claims 1-2, 7-8, 29 and 36 are drawn to the judicial exception of abstract ideas under Step 2A, Prong One.
This judicial exception is not integrated into a practical application because the only additional elements beyond the judicial exceptions recited in the claims is the Markush group of nephrogenic markers which can be relied on to identify the renal cell population and the expression of RACK-1 which amounts to more than insignificant extra-solution activity in the form of mere data gathering (See MPEP 2106.05(g)). Thus, the judicial exceptions are not integrated into a practical application under Step 2A, Prong Two.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the instant disclosure teaches limitations which are well-understood, routine, and conventional as it related to the Markush group of nephrogenic markers. The instant specification discloses on Pg. 6 that WNT9b is expressed as part of nephrogenic development in the ureteric bud and that WNT9b mediated induction in the cap mesenchyme initiates expression of WNT, FGF8, PAX8, and LHX1 genes and that those genes are not expressed in WNT9B-deficient animals which exhibit no development of nephrons. Further, the instant specification discloses on Pg. 52 that the transcription factor LHX1 is expressed early in the immediate mesoderm, is one of the first genes expressed in nephric mesenchyme, and that LHX1 depletion in Xenopus embryos results in near total loss of the kidney field and the prior art of Little as applied below teaches that LHX1 is an indicator of intermediate mesoderm cells which are developmental precursors to kidney cells. Similarly, the prior art of Padanilam and Hammerman as applied below teach that RACK-1 is a known marker of kidney cellular regeneration following injury. Thus, the additional element of LHX1 is a known nephrogenic marker and the additional element of RACK-1 is a known kidney cell regeneration marker and are no more than a well-understood, routine, and conventional limitation under Step 2B.
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 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.
Claims 1-2, 7-8, 48, 96, and 98 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 1 and 7 and 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 choose 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 combination 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.
With regard to claim 2, 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 claim 8, firstly, claim 8 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 being between about 8% to about 58% 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 8-58% of cells 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 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 8-58% 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 claim 48, as detailed above in claims 1 and 7, the combined teachings of Presnell and Little teach wherein presence of the nephrogenic marker LHX1 can be used to identify an enriched heterogeneous renal cell population as having therapeutic potential. 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 choose 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 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).
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.
Claims 29 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Presnell and Little as applied to claim 1 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 29, as detailed above in claim 1 and incorporated herein, 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.
With regard to claim 36, as detailed above, the combined teachings of Presnell, Little, and Padanilam and Hammerman teach an enriched heterogeneous renal cell population having therapeutic potential which can be identified by the presence of cells expressing LHX1 and RACK-1. 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 RACK-1 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 RACK-1 in a cell population, which the combined teachings of Presnell, Little, and Padanilam and Hammerman indicate can be used to identify cells which have increased proliferative ability and therefore therapeutic potential. Padanilam and Hammerman appear to demonstrate that nearly all of the kidney cells (i.e., at least about 85%) express RACK-1 mRNA five days after ischemia/hypoxia (See Fig 4). Since Presnell also teaches that generation of an enriched heterogeneous renal cell population comprises a hypoxic culture step, a skilled artisan would have expected similar amounts of RACK-1 cells in the enriched heterogenous renal cell population of Presnell.
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 and 96-97 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, and Stenvinkel. 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 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, 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. 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, and Stenvinkel, SRCs identified as expressing LHX1 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.
Conclusion
No claims are allowed.
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/ERIN V PAULUS/Examiner, Art Unit 1631
/ARTHUR S LEONARD/Examiner, Art Unit 1631