DETAILED ACTION
Applicant’s response filed 7/29/2026 has been received and entered into the application file. All arguments have been fully considered. Claims 1-8, and 10-12 are currently pending. Claims 1 and 12 are currently amended. Claim 9 is cancelled.
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 .
Specification – Objection Maintained
Applicant’s reply submitted 7/29/2026 indicates that the trade names will be properly capitalized, however no amendment to the specification has been received.
Applicant further notes that the trade names include proper symbols. However, it is noted that, for example, the trade name GlutaMAX is not accompanied by the appropriate trademark symbol (see specification at page 22, lines 4 and 12).
Claim Interpretation
Regarding claims 1-4, it is noted these claims are directed to a composition, per se.
Claim 1 has been amended to recite the following:
A composition comprising nephron progenitor extracellular vesicles (EVs), wherein the EVs are produced by a method comprising:
(a) engineering donor cells to express exogenous SNA/2, EYA1, and SIX1, thereby producing induced nephron progenitor (iNP) cells;
(b) culturing the iNP cells in a culture medium, thereby producing a conditioned medium; and
(c) collecting and purifying nephron progenitor EVs from the conditioned medium wherein the iNP cells express nephron progenitor markers SIX2 and CITED1.
As to the limitations directed to the manner by which the EVs are produced, such limitations are product-by-process limitations which appear to define the extracellular vesicles.
Claim 1 indicates the extracellular vesicles are produced by induced-nephron progenitor cells that express nephron progenitor markers SIX2 and CITED1 and the instant specification ([0084]) discloses the induced nephron progenitor cells are produced by re-programming HK2 cells (human proximal tubule epithelial cells) using SNAI2, EYA1 and SIX1 transcription factors.
The claims have been limited to reciting product-by-process limitations that indicate the extracellular vesicles are derived from cells that have been induced with the intracellular transcriptional factors SIX1, SNAI2, EYA1, SIX2 and CITED1 in order to produce cells having a nephron progenitor cell phenotype.
In looking to the specification to determine what distinct structural or chemical characteristics or properties are imparted to the product, by the recited process, it is noted that Applicant’s specification discloses the extracellular vesicles produced by the induced nephron progenitor cells (iNPs) have positive expression for the typical extracellular vesicle markers CD63, CD81, Alix, and TSG 101 (FIG. 3A; page 22, line 31 to page 23, line 8). Applicant’s specification does not further disclose any additional markers. Therefore, extracellular vesicles derived from native nephron progenitor cells would read on the claimed extracellular vesicles.
Further regarding claims 6-7 and the limitations directed to the donor cells, it is noted these limitations are likewise directed to the manner by which the claimed extracellular vesicles have been produced, and do not further limit the structure of the claimed extracellular vesicles.
REJECTION(S) WITHDRAWN
Claim Rejections - 35 USC § 112
Enablement:
RE: Rejection of Claims 5-11 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, enablement:
Applicant’s amendment submitted 7/29/2026 has amended claim 5 to remove the limitation directed to “preventing”, thus obviating the previous rejection of record.
Therefore, the rejection is withdrawn.
Written Description:
RE: Rejection of Claims 5-12 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:
Applicant’s amendment submitted 7/29/2026 has amended claim 5 to remove the limitation directed to “preventing” and claim 12 has been amended to recite ex vivo treatment, thus obviating the previous rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of Claims 1-4, 6-7 and 9 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite:
Regarding claim 1, the phrase "such as" has been removed, thus obviating the previous rejection of record.
Further regarding claim 1, the limitation “nephron progenitor-like cells” has been removed.
Claim 9 has been cancelled.
Therefore, the previous rejection of record is withdrawn.
Claim Rejections - 35 USC § 102
RE: Rejection of Claim 1 under 35 U.S.C. 102(a)(1) as being anticipated by Kumar et al., (Oncotarget, 2014 oct 28;6(5):3280-3291:
The rejection is withdrawn in view of Applicant’s amendment submitted 7/29/2026.
RE: Rejection of Claims 1-2 and 4-8 under 35 U.S.C. 102(a)(1) as being anticipated by Yu et al:
The rejection is withdrawn in view of Applicant’s amendment submitted 7/29/2026.
Claim Rejections - 35 USC § 103
RE: Rejection of Claim 2 under 35 U.S.C. 103 as being unpatentable over Kumar:
The rejection is withdrawn in view of Applicant’s amendment submitted 7/29/2026.
RE: Rejection of Claims 3-4 under 35 U.S.C. 103 as being unpatentable over Kumar, and further in view of Saari:
The rejection is withdrawn in view of Applicant’s amendment submitted 7/29/2026.
RE: Rejection of Claim 3 under 35 U.S.C. 103 as being unpatentable over Yu, in view of Goggins:
The rejection is withdrawn in view of Applicant’s amendment submitted 7/29/2026.
RE: Rejection of Claims 9 and 11 under 35 U.S.C. 103 as being unpatentable over Yu, in view of Marants:
The rejection is withdrawn in view of Applicant’s amendment submitted 7/29/2026.
RE: Rejection of Claims 10 and 12 under 35 U.S.C. 103 as being unpatentable over Yu, in view of Mehrotra:
The rejection is withdrawn in view of Applicant’s amendment submitted 7/29/2026.
REJECTION(S) MAINTAINED/UPDATED
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 1-4 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
The rationale set forth below conforms to current Office practice for examination of claims under § 101.
These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. All of the claims are directed to a statutory category, e.g., a composition (Step 1: YES).
The next part of the analysis involves whether the claimed invention recites or is directed to one or more judicial exceptions (Step 2A, prong one).
Claim 1: Claim 1 is directed to a composition comprising extracellular vesicles (EVs) that are derived from induced nephron progenitor cells.
As discussed above at Claim Interpretation, the claimed extracellular vesicles encompass naturally occurring extracellular vesicles produced by native nephron progenitor cells (see Kwon at Figure 1; page 472 at Renal regeneration capacity of EVs, left col; IDS 4/5/2024). Additionally, it is noted the specification identifies the extracellular vesicles as having expression of typical, native exosomal markers, such as CD63, CD81, Alix, and TSG 101 (FIG. 3A), and Creative Biolabs, Exosome Marker related Antibody Products (previously cited), evidences the indicated markers are classic exosomal markers (see Overview).
Thus, the extracellular vesicles as currently claimed read on native extracellular vesicles.
The claim as a whole, considering all claim elements, does not amount to significantly more than the natural product of extracellular vesicles produced by native nephron progenitor cells. Accordingly, claim 1 is directed to an exception (Step 2A, prong one: YES).
Regarding claims 2-4, it is noted these claims recite additional features that further define the extracellular vesicles by their native size or additional elements that encompass additional natural products such as inhibitory RNA (therapeutic agent) and saline carrier. However, these limitations do not limit the claimed extracellular vesicles in such a way that provides a markedly different structure or biological and/or pharmacological function to the extracellular vesicles that is not present in the natural counterpart.
Thus, the claimed composition does not have markedly different characteristics from what occurs in nature and is a "product of nature" exception. Thus, the claims do not qualify as eligible subject matter and are rejected under 35 U.S.C. 101.
Accordingly, the claims are directed to an exception (Step 2A, prong one: YES). Thus, the claims do not qualify as eligible subject matter and are rejected under 35 U.S.C. 101.
The next part of the analysis involves whether the claimed invention recites additional elements that integrate the judicial exception into a practical application (Step 2A, prong two).
Given the claims are directed to a composition, the claims do not recite additional steps that integrate the judicial exception into a practical application (Step 2A, prong two: No).
The final part of the analysis involves whether the claimed invention, as a whole, recite something “significantly more” than the judicial exceptions (Step 2B).
In view of the above and considered as a whole, the claimed composition does not have markedly different characteristics from what occurs in nature and such elements discussed above are not significantly more than the indicated judicial exceptions. Thus, the claims do not qualify as eligible subject matter and are rejected under 35 U.S.C. 101 (Step 2B: NO).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kwon et al., (previously cited, see IDS 4/5/2024) (“Kwon”).
Regarding claim 1, Applicant’s amendment submitted 7/29/2026 has amended claim 1 to require the composition comprises nephron progenitor extracellular vesicles (EVs).
As set forth above at Claim Interpretation, in consideration of the process employed to produce the claimed EVs, it is noted that extracellular vesicles derived from native nephron progenitor cells would read on the claimed extracellular vesicles.
Kwon, Figure 1, discloses that EV’s released by progenitor cells in the nephron (i.e., nephron progenitor cells) are effective for regenerating injured epithelial cells, thus limiting renal damage. Thus, Kwon’s Figure 1 discloses a composition comprising nephron progenitor extracellular vesicles, thus anticipating claim 1.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Kwon, as applied to claim 1 above.
The teaching of Kwon is set forth above.
Regarding claim 2, Kwon does not specifically exemplify the extracellular vesicles have an average diameter of 50-150 nm. However, Kwon teaches that extracellular vesicles (EVs) refer to all membrane-bound vesicles released from cells into the extracellular space and include exosomes, microvesicles, microparticles, ectosomes, and oncosomes (Introduction, left col, page 470), and the instant specification ([0065]) discloses that microvesicles have a broad range of diameters and functions, including apoptotic bodies (1-5 μm), microvesicles (100-1000 nm in size), and exosomes (50-150 nm).
Thus, given that Kwon’s extracellular vesicles also comprise exosomes, as disclosed in the instant specification, it is reasonable to consider Kwon’s disclosed exosomes have a substantially similar diameter ranging in size of 50-150 nm. Thus, the claimed range overlaps the prior art range.
In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05
NEW GROUND(S) OF REJECTION, NECESSITATED BY AMENDMENT
Claim(s) 3-8 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al., (previously cited) (“Yu”), in view of Kwon et al., (previously cited) and Sun et al., (Stem Cell Research & Therapy (2019) 10:8, 9 pages; see PTO-892) (“Sun”).
It is noted that claim 5 recites a method of treating acute kidney injury in a subject, comprising administering to the subject an effective amount of the composition of claim 1.
Applicant’s amendment submitted 7/29/2026 has limited the composition of claim 1 to nephron progenitor extracellular vesicles (EVs), and as noted above at Claim Interpretation, in consideration of the process employed to produce the claimed EVs, it is noted that extracellular vesicles derived from native nephron progenitor cells would read on the claimed extracellular vesicles.
Regarding claims 4-5 and 8, Yu teaches extracellular vesicles (EVs) obtained from embryonic stem cells (ESCs) have therapeutic potential and are considered an alternative to embryonic stem cell-based therapies. Yu teaches administering extracellular vesicles obtained from embryonic stem cells (ESC-EVs) for treating acute kidney injury (AKI), wherein the ESC-EVs promoted recovery of the damaged kidney (i.e., administered after the onset of the injury, claim 8), promoted proliferation of renal tubular epithelial cells, facilitated renal angiogenesis, inhibited fibrosis, and rescued DNA damage (Abstract, entirety; Fig. 2A). Yu teaches the ESC-EVs had positive expression of the exosomal markers Alix and TSG101 (Fig. 1A), had a size of approximately 80 nm (page 5, right col). Yu teaches the ESC-EVs were administered 45 minutes after the onset of injury and in PBS (i.e., pharmaceutically acceptable carrier, claim 4) at a concentration of 100 µg per injection (i.e., effective amount) (page 3 at AKI model).
Yu does not further teach the EVs are sourced from nephron progenitor cells, as recited in 5. However, Kwon, at Figure 1, discloses that EV’s released by progenitor cells in the nephron (i.e., nephron progenitor cells) are effective for regenerating injured epithelial cells, thus limiting renal damage, and Sun further teaches that endogenous renal stem/progenitor cell-derived EVs have beneficial effects in repairing kidney damage (page 5, right col, third para) and specifically notes that resident (endogenous) nephrogenic EVs contribute to recovery from AKI (page 5, right col, third and fourth para.).
Therefore, it is submitted that because each of the types of EVs disclosed by Yu, Kwon and Sun were known to treat acute kidney injury (AKI), it would further have been obvious to one having ordinary skill in the art to combine the nephron progenitor-derived EVs of Kwon and Sun with the EVs of Yu for the purpose of producing a therapeutic EV composition that promotes treating acute kidney injury. Combination of multiple products (i.e. EVs) each known to have the same effect to produce a final product having the same effect is prima facie obvious. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
The person of ordinary skill in the art would have been motivated to modify the therapeutic EV composition of Yu to include nephron progenitor-derived EVs, as taught by Kwon, for the predictable result of successfully promoting treatment of acute kidney injury, thus meeting the limitations of claims 4-5 and 8.
The skilled artisan would have had a reasonable expectation of success in combining the teachings of Yu with Kwon and Sun because each of these teachings are directed at using EVs to promote treatment of acute kidney injury.
Regarding claim 3, Kwon teaches the EVs comprise small RNAs that confer the therapeutic protective effect in the ischemic kidney after the acute kidney injury (page 472, left col, last para), thus meeting the limitation of claim 3.
Further regarding claims 6-7, it is noted as set forth above at Claim Interpretation, the limitations directed to the donor cells, are directed to the manner by which the claimed extracellular vesicles have been produced, and do not further limit the structure of the claimed extracellular vesicles. Therefore, claims 6-7 are included in the rejection of claim 5.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Yu, in view of Kwon and Sun, as applied to claims 3-8 above, and further in view of Marants et al., (JASN 30: 1086–1095, 2019; previously cited) (“Marants”).
The teaching of Yu, in view of Kwon and Sun, is set forth above.
Regarding claim 11, it is noted that Yu, in view of Kwon and Sun, does not further teach the composition is administered to a subject undergoing dialysis (claim 11). However, Marants teaches of a study showing there is an acute decrease in renal perfusion during hemodialysis (kidney dialysis), which is a first step toward pathophysiologic characterization of hemodialysis-mediated residual renal function (RRF) decline, and suggest further study is needed to explore the potential of dialysate cooling as a therapeutic approach to slow RRF decline (Abstract, entirety).
Marants teaches it is known that hemodialysis (HD) causes recurrent renal ischemic insults, which may cause irreversible injury leading to residual renal function (RRF) loss (page 1087, left col, third para). Marants further teaches of AKI risk as a result of repeated hemodialysis and resulting renal tubular damage (page 1092, left col, second full para).
Thus, Marants has established it was known that patients undergoing kidney dialysis are at risk of AKI. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to conduct treatment to subjects undergoing kidney dialysis.
The person of ordinary skill in the art would have been motivated to modify the treatment method of Yu, in view of Kwon and Sun, to include treatment of dialysis patients for the predictable result of reducing the risk of acute kidney injury in patients receiving routine hemodialysis, thus meeting the limitation of claim 11.
The skilled artisan would have had a reasonable expectation of success in combining the teachings of the combined prior art and Marants because each of these teachings are directed at renal therapies.
Claims 10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Yu, in view of Kwon and Sun, as applied to claims 3-8 above, and further in view of Mehrotra et al., (Am J Kidney Dis. 2012;59(4):558-565; previously cited) (“Mehrotra”).
The teaching of Yu, in view of Kwon and Sun, is set forth above.
Regarding claims 10 and 12, it is noted that Yu, in view of Kwon and Sun, does not further teach treating a subject that is the recipient of a kidney transplant (claim 10), or the treatment of the donor kidney prior to transplantation (claim 12). However, Mehrotra is directed to the incidence and consequences of acute kidney injury (AKI) in kidney transplant recipients and teaches that AKI was associated independently with increased risk of transplant loss, and concludes that AKI is increasingly common and associated with transplant failure and death (Abstract, entirety).
Thus, Mehrotra has established it was known that patients receiving a donor kidney via a kidney transplant are at risk of AKI and AKI was associated independently with increased risk of transplant loss. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat donor kidneys and the transplant subjects with the therapeutic ESC-EVs.
The person of ordinary skill in the art would have been motivated to modify the treatment method of the combined prior art to include treating donor kidneys and the transplant subjects for the predictable result of reducing the risk of acute kidney injury and promoting restoration of the structure and function of the injured kidney and reducing transplant failure, thus meeting the limitation of claims 10 and 12.
The skilled artisan would have had a reasonable expectation of success in combining the teachings of the combined prior art and Mehrotra because each of these teachings are directed at renal therapies.
Response to Remarks:
Rejection under 35 USC 101:
Applicant asserts that the induced nephron progenitor cells (iNP) are not naturally occurring since the iNPs are produced by inducing expression of the recited transcription factors in a parent cell line (HK2 cells), thus resulting in cells having a nephron progenitor phenotype, as discussed at Applicant’s remarks (page 6).
Applicants further assert the EVs produced from the induced nephron progenitor cells have markedly different characteristics from naturally occurring EVs derived from nephron progenitor cells and notes the proteomic analysis shows increased expression of many proteins as indicated at FIG 3E, as discussed at Applicant’s remarks (page 6).
Applicant’s remarks have been fully considered but are not found persuasive since the data presented at FIG 3E does not provide any experimental data comparing EVs derived from the induced nephron progenitors to EVs derived from naturally occurring nephron progenitors. FIG 3E shows expression data of only iNP-derived EVs.
It is additionally noted that Applicant’s specification only shows the iNP-derived EVs expressing classical exosome markers.
Rejections under 35 USC 102 and 103:
Applicant asserts that the process of preparing induced nephron progenitor cells would impart distinct structural characteristics to the resulting EVs. Applicant points to the proteomic analysis of FIG 3E, as discussed at Applicant’s remarks (page 7).
Applicant further points to Kwon’s teaching at page 472 and asserts that Kwon’s disclosed EVs are not derived from cells engineered to comprise a nephron progenitor phenotype, as discussed at Applicant’s remarks (page 8).
Applicant’s remarks have been considered but are not found persuasive since the proteomic data does not provide any comparison to the prior art native EVs derived from nephron progenitor cells. Applicant’s FIG. 3A shows the resulting EVs having classical EV (exosome) markers and no further evidence has been provided to show that EVs derived from induced nephron progenitor cells have a marker profile that is substantially different from native nephron progenitor cells.
Secondly, as set forth at Claim Interpretation, in consideration of the process employed to produce the claimed EVs, it is noted that extracellular vesicles derived from native nephron progenitor cells would read on the claimed extracellular vesicles, absent evidence to the contrary.
Conclusion
No claim is allowed. No claim is free of prior art.
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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to E. YVONNE PYLA whose telephone number is (571)270-7366. The examiner can normally be reached M-F 9am - 6pm.
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/EVELYN Y PYLA/ Primary Examiner, Art Unit 1633
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