DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/23/2025 has been entered.
Claim 74 has been amended. Claim 95 has been newly added and no claims have been newly canceled.
Claims 74-78 and 85-95 are currently pending and have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 74-78, 85-88, 92-95 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Atala et al (US 2005/0002915-newly cited and hereinafter referred to as Atala ‘915) in view of Tumlin et al (Journal of the American Society of Nephrology, published May 2008-from IDS filed 11/20/2024) and Hsu et al (Kidney International, 2001-newly cited).
Regarding claims 74, 76-78, 85-87 and 95, Atala ‘915 disclose methods of treating subjects with a kidney disorder by administering an isolated population of renal cells derived from a kidney biopsy to augment kidney function (page 3 para 22, para 24). Kidney cell types include proximal tubules, distil tubules, and collecting ducts (page 3 para 24-25). One embodiment specifically includes isolated population of tubule cells to augment and ameliorate a tubular disorder (page 21 para 208).
Atala ‘915 do not specifically disclose wherein their selected renal cells are enriched for renal tubular cells and depleted of EPO-producing glomerular and vascular cells.
Tumlin teach that renal tubular cell therapy provides beneficial results for patients suffering from acute renal failure. The primary effect was to improve overall patient survival and earlier renal recovery which was associated with long term survival benefit (page 5 Discussion).
One of ordinary skill in the art would have been motivated to include renal tubular cells in an enriched amount in the method of Atala ‘915 because Tumlin teach that renal tubular cells are beneficial for the treatment of acute renal failure and Atala ‘915 is directed toward the administration of renal cells for the treatment of kidney disease as well. The isolation and enrichment of tubular cells would deplete the renal cell population of EPO-producing cells such as glomerular and vascular cells and Atala ‘915 indicates that mixed cell populations are optional and not required. One of ordinary skill in the art would have had a reasonable expectation of success because Atala ‘915 also include an embodiment wherein an isolated population of tubular cells are to be administered (page 21 para 208).
Atala ‘915 do not specifically disclose determining in a biological sample from the subject that a level of an erythropoiesis indicator is different from the level of this indicator in a control.
Hsu disclose that there is a relationship between hematocrit and renal function in men and women (Title). Hsu disclose that a decrease in hematocrit is apparent even among patients with mild to moderate renal insufficiency (page 725, column 1, page 730 column 2). Hematocrit is measured from serum samples and recognized to change as a result of acute illness requiring multiple measurements more than a week apart (page 725, column 2, paragraph bridging pages 726-727).
One of ordinary skill in the art would have been motivated to measure and observe the subject’s serum hematocrit (an erythropoiesis indicator) in the method of Atala ‘915 because Hsu teach and suggest that there is a relationship between a relationship between hematocrit and renal function in men and women and that hematocrit changes can be expected to change as a result of acute illness as well as mild to moderate renal insufficiency. One of ordinary skill in the art would have been motivated to measure and observe hematocrit before and after any treatment in order to determine if such treatment made a difference in the severity of the kidney disfunction as reflected by the hematocrit. One of ordinary skill in the art would have had a reasonable expectation of success because both Atala ‘915 and Hsu are directed to the analysis and treatment of kidney disfunction.
This renders obvious the measuring of hematocrit from a serum sample of the subject both before and after administration of the cells in order to evaluate the hematocrit status of the patient. A hematocrit measurement from a serum sample before the cell administration is performed reads on the limitation of a control. Although neither Hsu nor Atala specifically identify performing these hematocrit measuring steps as a way of determining erythroid homeostasis in the subject, the performance of these steps, even for a different reason, will read upon this claim limitation.
Regarding claim 75, Atala ‘915 disclose wherein the cells used are autologous to the subject (pages 1-2 para 11-12).
Regarding claim 88, Atala ‘915 disclose wherein the renal cells for administration can also include kidney and epithelial cells (pages 1-2 para 11) and kidney cells from the collecting duct (page 3 para 25). Since glomeruli cells are not required an embodiment without them is an option and therefore obvious.
Regarding claims 92-93, Atala ‘915 disclose wherein the cells are suspended in a pharmaceutically acceptable carrier, including a hydrogel which contains water (page 2 para 12, pages 2-3 para 20-22, para 24, para 30, page 5 para 47).
Regarding claim 94, Atala ‘915 disclose that the cell suspension can be injected at the target site (page 2 para 12) and the intended target of the renal cells is the kidney.
Therefore, the combined teachings of Atala ‘915, Tumlin et al and Hsu et al render obvious Applicant’s invention as claimed.
Claims 89-90 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Atala et al (US 2005/0002915-newly cited and hereinafter referred to as Atala ‘915) in view of Tumlin et al (Journal of the American Society of Nephrology, published May 2008-from IDS filed 11/20/2024) and Hsu et al (Kidney International, 2001-newly cited) as applied to claims 74-78, 85-88, 92-95 above, and further in view of Turman et al (Biochemical and Molecular Medicine, 1997-newly cited).
Regarding claims 89-90, the combined teachings of Atala ‘915, Tumlin et al and Hsu et al render obvious Applicant’s invention as described above, but do not specifically disclose wherein the enriched renal cell population is hypoxia-resistant.
Turman disclose a primate model of hypoxic preconditioning in which exposure of primary cultures of human proximal tubular epithelial cells (PTEC) to sublethal hypoxia induces resistance for subsequent hypoxic injury (page 50, column 2). Hypoxic preconditioning in PTEC may not be mediated by increased heat shock proteins (HSP), the presence of an abundant of constitutively expressed HSP may be essential for cell survival and recovery from hypoxia (page 56, column 1).
One of ordinary skill in the art would have been motivated to utilize enriched renal cell populations in the method of Atala ‘915 that were hypoxia resistant because Turman teach and suggest that this provides increased cell survival to renal tubular cells. One of ordinary skill in the art would have had a reasonable expectation of success because Atala ‘915 and Turman are both directed to the use of renal tubular cells and Turman demonstrate that cultured human proximal tubular cells become resistant to hypoxic injury when exposed to hypoxic preconditioning.
Therefore, the combined teachings of Atala ‘915, Tumlin et al, Hsu et al and Turman et al render obvious Applicant’s invention as claimed.
Claim 91 is are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Atala et al (US 2005/0002915-newly cited and hereinafter referred to as Atala ‘915) in view of Tumlin et al (Journal of the American Society of Nephrology, published May 2008-from IDS filed 11/20/2024) and Hsu et al (Kidney International, 2001-newly cited) as applied to claims 74-78, 85-88, 92-95 above, and further in view of Goodwin et al (US 2005/0064443).
Regarding claim 91, the combined teachings of Atala ‘915, Tumlin et al and Hsu et al render obvious Applicant’s invention as described above, and Atala ‘915 specifically teach and suggest using unique markers to select for a cell type (page 33 para 343), but do not specifically disclose wherein the enriched renal cell population express one or more of megalin, cubilin, and hyaluronic acid synthase 2.
Goodwin teach that specific markers for renal tubular cells include megalin and cubilin (page 8 para 94).
One of ordinary skill in the art would have been motivated to use the unique markers of megalin and/or cubilin in the method of Atala ‘915 to select for the desired renal cell type of tubular cells for enrichment because Goodwin teach and suggest that these are markers for this renal cell type and Atala ‘915 suggest that using markers specific to the desired cell type is beneficial and desirable for selection. One of ordinary skill in the art would have had a reasonable expectation of success because Atala ‘915 specifically teach the benefit of using unique markers to select for a cell type (page 33 para 343), Tumlin teach that renal tubular cells are beneficial for the treatment of acute renal failure and Atala ‘915 is directed toward the administration of renal cells for the treatment of kidney disease as well.
Therefore, the combined teachings of Atala ‘915, Tumlin et al, Hsu et al and Goodwin et al render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant’s arguments with respect to claim(s) 74-78 and 85-95 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Madsen et al., “Phagocytosis of erythrocytes by the proximal tubule of the rat kidney”, Cell and Tissue Research, (1982), Vol. 226, pp. 363-374.
Madsen disclose the interaction between renal tubular cells and erythrocytes.
Mimura et al., “Erythrophagocytosis by renal tubular cells”, Kidney International, published August 01, 2008, Vol. 74, P398, page 1.
Mimura disclose the interaction between renal tubular cells and erythrocytes.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Doug) Schultz can be reached on 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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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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