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 .
Status of the Claims
Applicant' s submission filed 26 June 2026 has been entered. Claims 1-6, 9-12, and 15 are pending. Claims 1, 3, 5, 10, and 15 have been amended, while claims 7-8 and 13-14 have been cancelled without prejudice or disclaimer. Therefore, prosecution on the merits continues for claims 1-6, 9-12, and 15. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Objection to the Specification
The substitute Specification filed 26 June 2026 is acknowledged and entered into the application file. With that, Applicant’s amendments to the Abstract obviate the objection of record.
Therefore, the objection is withdrawn.
RE: Objection to claims 7-8 and 13-14
The cancellation of claims 7-8 and 13-14 renders the objections of record moot. It is of note that Applicant has corrected the minor informalities within claims 1 and 10 as written.
Therefore, the objections are withdrawn.
RE: Rejection of claim 9 under 35 USC 112(b)
Applicant’s amendments to parent claim 1 correct the antecedent basis, thus obviating the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claim 9 under 35 USC 112(d)
Applicant’s amendments to instant claim 9 correct the dependency of the claim, thus obviating the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1-6 and 10-12 under 35 USC 103 over Das in view of Nakajima et al
Applicant has amended independent claims 1 and 10 to require the quality control substance to be a suspension of squamous epithelial cells derived from a mammal, as well as the squamous epithelial cells derived from a mammal to be mucosal epithelial cells derived from a human oral cavity (previous claims 7, 13), or surface mucous cells derived from a bovine stomach, a cervine stomach, a sheep stomach, or a porcine stomach (previous claims 8, 14). As claims 7-8 and 13-14 were not included within the rejection of record, Applicant’s amendments obviate the rejection.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1-7 and 10-13 under 35 USC 103 over Das in view of Nakajima et al and Hustler et al
The cancellation of claims 7 and 13 renders the rejection moot for those claims. For the remaining claims, Applicant’s arguments filed 26 June 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Pages 7-8 of the Remarks filed 26 June 2026 that the disclosures of Das, Nakajima et al, and Hustler et al fail to disclose or suggest using a suspension of squamous epithelial cells derived from a mammal as a quality control substance. In response, the Examiner respectfully submits that Das teaches a suspension of quality control cells. See, for example, Paragraphs [0033], [0053]-[0081] of Das. Therefore, the ordinary artisan would have recognized that the quality control mucosal epithelial cells derived from human buccal tissue as taught by Das in view of Nakajima et al and Hustler et al can be comprised within a suspension.
Applicant has further traversed the rejection, asserting in Page 8 of the Remarks filed 26 June 2026 that Hustler et al fail to compare the morphology of individual normal human buccal epithelial (NHB) cells to normal human urothelial (NHU) cells, instead comparing sheets of the respective cells. In response, the Examiner respectfully submits that Hustler et al do sufficiently compare the morphology of individual NHB cells to NHU cells such that the ordinary artisan would have recognized they are reasonably similar. See, for example, Figures 1C-D of Hustler et al.
Therefore, the rejection is maintained and amended to encompass the claims as currently written.
RE: Rejection of claims 1-15 under 35 USC 103 over Das in view of Nakajima et al, Hustler et al, and Xu et al
The cancellation of claims 7-8 and 13-14 renders the rejection moot for those claims. For the remaining claims, Applicant’s arguments filed 26 June 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Pages 8-9 of the Remarks filed 26 June 2026 that Xu et al fail to compare the morphology of individual human buccal epithelial cells to omasal epithelial cells (OECs), instead comparing clusters and monolayers of the respective cells. In response, the Examiner respectfully submits that Xu et al do sufficiently compare the morphology of individual human buccal epithelial cells to OECs such that the ordinary artisan would have recognized they are reasonably similar. See, for example, Figures 2 and 6 of Xu et al.
Therefore, the rejection is maintained and amended to encompass the claims as currently written.
Maintained Grounds of Rejection
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.
Claims 1-6 and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Das (US 2020/0371086 A1, of record on IDS filed 24 May 2023) in view of Nakajima et al (US 2019/0101742 A1, of record on IDS filed 24 May 2023) and Hustler et al (Exp Cell Res, 2018, of record).
Das is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2), with a publication date of 26 November 2020. Nakajima et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2), with a publication date of 04 April 2019 – which is greater than one year prior to the effective filing date of the instant invention. Hustler et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 1-2: Das discloses quality control substances for use with a microscopy-based urine sediment analyzer, as well as methods of improving the detection of an analyte in a urine sample from a subject by using the quality control substances (Abstract; Paragraphs [0002], [0004]-[0006], [0016]-[0018], [0028], [0083]).
As such, Das discloses that common sediments found within urine and indicative of pathological conditions include red blood cells, white blood cells, crystals, bacteria, yeast, pathological casts, or non-squamous epithelial cells (Paragraphs [0027]-[0028], [0043]). Das further discloses within an embodiment of the invention that yeast cells in suspension can be included in the quality control substance to serve as a morphological control for yeast present in a urine sample (Paragraphs [0034], [0041], [0043], [0045], [0072]). In another embodiment, Das further discloses that human cancer cells in suspension can be a quality control substance to serve as a morphological control for non-squamous epithelial cells present in a urine sample (Paragraphs [0032], [0036]-[0039], [0047]-[0066]).
Das further discloses that the quality control substances are morphologically matched to the sedimentary analytes found within the analyzed urine samples (Paragraphs [0003], [0005], [0032]-[0035], [0038], [0071]).
Das does not disclose that the quality control substance is squamous epithelial cells derived from a mammal, nor that the squamous epithelial cells cell controls are mucosal epithelial cells derived from a human oral cavity, as required by instant claim 1.
In regards to the quality control substance being derived from a mammal, Nakajima et al disclose the testing of urine for analytes using an analysis apparatus, wherein the analytes include an erythrocyte, a leukocyte, a squamous epithelial cell, other epithelial cells, a cast, a crystal, and a bacterium (Abstract; Paragraphs [0025], [0060]-[0066]).
Therefore, it would have been prima facie obvious to have modified the urinalysis method of Das such that the presence of squamous epithelial cells is detected within a urine sample using a squamous epithelial cell as a quality control substance, as detailed in Nakajima et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to analyze a well-known analyte within urine samples utilizing a morphologically identical quality control substance – i.e., the same cell type – and would have had a reasonable expectation of success given that the disclosures of Das and Nakajima et al are both concerned with the analysis of sediment within urine samples. More specifically, the ordinary artisan would have reasonably understood that mammalian squamous epithelial cells can serve as a quality control substance for squamous epithelial cells in urine given the sedimentary squamous epithelial cell parameters provided in Nakajima et al (Paragraphs [0060]-[0066]). See MPEP § 2143(I)(G).
In regards to the squamous epithelial cells cell controls being mucosal epithelial cells derived from a human oral cavity, Hustler et al disclose that squamous epithelial cells derived from the buccal mucosa of human subjects are essentially morphologically identical to human urothelial cells (Pages 284-286, 288, 293; Figure 1).
Therefore, it would have been prima facie obvious to have modified the urinalysis method of Das in view of Nakajima et al such that the squamous epithelial cell quality control substances are mucosal epithelial cells derived from human buccal tissue, as suggested in Hustler et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to utilize a squamous epithelial cell that is morphologically matched to the urothelial cells found in urine, and would have had a reasonable expectation of success given the outlined protocols in Das relating to the usage of quality control substances that are morphologically matched to the sedimentary counterparts. See MPEP § 2143(I)(G).
Consequently, Das as modified by Nakajima et al and Hustler et al render obvious a method of analyzing urine with a microscopy-based urine sediment analyzer utilizing a suspension of mammalian squamous epithelial cells as a quality control substance to improve the detection accuracy (claim 2). As the squamous epithelial cell quality control substance is mucosal epithelial cells derived from human buccal tissue, this therefore renders obvious the method of instant claim 1.
Regarding claims 3-5: Following the discussion of claim 1, Das further discloses that the quality control substances are fixed (claim 5) and stored in phosphate-buffered saline (claims 3-4) (Paragraphs [0032], [0058]-[0064]). This therefore reads on the methods of the instant claims.
Regarding claim 6: As aforementioned in the discussion of claim 1, Das discloses that the epithelial cell quality control substances can be derived from humans (Paragraphs [0032], [0057]-[0059]). This therefore reads on the method of the instant claim.
Regarding claims 10-11: As aforementioned in the discussion of claim 1, Das as modified by Nakajima et al and Hustler et al render obvious a method of analyzing urine with a microscopy-based urine sediment analyzer utilizing mucosal epithelial cells derived from human buccal tissue as a quality control substance to improve the detection accuracy.
Nakajima et al further disclose that the urine sediment analyzer is capable of counting the number of sediment components within a urine sample (Paragraphs [0005], [0007], [0084]-[0087], [0095]-[0096], [0100], [0106]-[0108], [0112]-[0113]).
Therefore, it would have been prima facie obvious to have modified the urinalysis method of Das such that the concentration of a mammalian squamous epithelial cell control is measured and then utilized as a reference to the concentration of sedimentary squamous epithelial cell in a urine sample, as suggested in Nakajima et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to determine and enhance the accuracy of the measured samples by comparing them to a known reference value, and would have had a reasonable expectation of success given the counting protocols outlined in Nakajima et al. See MPEP § 2143(I)(G).
Consequently, Das as modified by Nakajima et al and Hustler et al render obvious a method of analyzing a urine sample (claim 11), wherein a concentration of a mammalian squamous epithelial cell quality control substance is measured and then utilized as a reference to the concentration of sedimentary squamous epithelial cell within the urine sample. As the squamous epithelial cell quality control substance is mucosal epithelial cells derived from human buccal tissue, this therefore renders obvious the method of instant claim 10.
Regarding claim 12: As aforementioned in the discussion of claim 10, Das discloses that the epithelial cell quality control substances can be derived from humans (Paragraphs [0032], [0057]-[0059]). This therefore reads on the method of the instant claim.
Claims 1-6, 9-12, and 15 remain rejected under 35 U.S.C. 103 as being unpatentable over Das (US 2020/0371086 A1, of record on IDS filed 24 May 2023) in view of Nakajima et al (US 2019/0101742 A1, of record on IDS filed 24 May 2023) and Hustler et al (Exp Cell Res, 2018, of record), and further in view of Xu et al (PLoS One, 2014, of record).
The discussion of Das as modified by Nakajima et al and Hustler et al regarding claims 1 and 10 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Das as modified by Nakajima et al and Hustler et al render obvious claims 1-6 and 10-12. Xu et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 9 and 15: As aforementioned in the discussion of claims 1 and 10 above, Das as modified by Nakajima et al and Hustler et al render obvious a method of analyzing a urine sample, wherein the squamous epithelial cell quality control substances are mucosal epithelial cells derived from human buccal tissue.
Hustler et al further disclose that the buccal-derived mucosal epithelial cells are approximately 50 microns in size, exhibit a ‘cobblestone’ appearance, and comprise a dark-round nucleus (Pages 286-288; Figure 1C).
The combination of Das, Nakajima et al, and Hustler et al fail to teach that squamous epithelial cell quality control substances are surface mucous cells derived from a bovine omasum, as required by instant claims 9 and 15.
Xu et al, however, disclose that surface omasal epithelial cells are approximately 50 microns in size, exhibit a typical ‘cobblestone’ appearance, and comprise a dark-round nucleus (Pages 1-3, 6-7; Figures 2-3, 6).
Therefore, it would have been prima facie obvious to have substituted the buccal-derived mucosal epithelial cell quality controls of Das as modified by Nakajima et al and Hustler et al with the surface omasal epithelial cells of Xu et al, as doing so would have been a simple substitution of one morphologically matched squamous epithelial cell control for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two cell types are functionally comparable, as both the buccal- and omasal-derived squamous epithelial cells comprise the same morphological characteristics, and thereby would have been able to substitute the two cell types with predictable results.
Consequently, Das as modified by Nakajima et al, Hustler et al, and Xu et al render obvious a method of analyzing a urine sample, wherein the squamous epithelial cell quality control substances are surface mucosal epithelial cells derived from bovine omasum (claims 9 and 15). This therefore renders obvious the methods of the instant claims.
Conclusion
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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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