Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's submission filed on 1 Sept. 2026 has been entered.
Claims 1, 4, 6, 7, 11 and 14-24 are currently pending and are considered here.
Any rejection not reiterated herein has been withdrawn.
Response to Arguments
Applicant's arguments filed 1 Sept. 2026 have been fully considered but they are not persuasive.
Regarding the anticipation rejection, Applicant argues that Metzger’s disclosure of bladder cancer does not anticipate urothelial carcinoma because bladder cancer encompasses other types of malignancies. Applicant cites a WebMD article in support, said to be submitted with the response. The WebMD article does not appear to have been submitted with the response. The argument is further unpersuasive because Lenis states that “Bladder cancer is a carcinoma of the urothelial, or “umbrella,” cells that line the lumen of the urinary bladder. Technically, urothelial carcinoma includes tumors of the bladder, upper urinary tract (renal pelvis and ureters), and proximal urethra. Bladder cancer accounts for approximately 90% to 95% of urothelial carcinoma” (p. 1981, under Pathophysiology and Molecular Biology). Thus, Lenis evidences that bladder cancer is a type/species of urothelial carcinoma, and as such the disclosure of bladder cancer anticipates urothelial carcinoma (see MPEP 2131.02, I. - teaching of a species within a genus anticipates the genus). Moreover, even if one might argue that “bladder cancer” constitutes a genus that does not fall entirely within the umbrella of “urothelial carcinoma”, a generic disclosure anticipates a claimed species when one of ordinary skill in the art would “at once envisage” the claimed species. Lenis evidences that “Bladder cancer accounts for approximately 90% to 95% of urothelial carcinoma” (see above), and thus one of ordinary skill in the art would at once envisage urothelial carcinoma from the disclosure of bladder cancer.
Applicant further argues that the disclosure of Metzger is non-enabling with respect to the claimed method since it does not disclose any experiments/examples demonstrating the detection of active PKCα in urine to diagnose cancer. This is not persuasive because Metzger teaches detection via the same means as recited in the instant claims, i.e. by contacting urine with an antibody or substrate peptide for the active form of PKCα. Applicant has not provided any specific reasoning why the teachings of Metzger would not be effective for measuring active PKCα in urine or why undue experimentation would be required. For example, Applicant has not pointed to any specific steps required for detection of active PKCα in urine that are not taught by Metzger. The lack of working examples is not sufficient to show lack of enablement (see MPEP 2164.02).
Regarding the 103 rejection, Applicant argues that the specification establishes unexpected results relating to the high level of sensitivity and accuracy for urine PKCα relative to other urothelial carcinoma markers (citing Table 1 of the specification). This is not persuasive because Applicant has not provided sufficient information to determine that the results are in fact unexpected and unobvious and of both statistical and practical significance, as required to establish unexpected results (see MPEP 716.02(b)). For example, Applicant has not provided context about the comparisons made in Table 1 (e.g., why the comparative markers would be representative of the state of the art, how the thresholds and other bases for comparison were selected, etc.) and why the results shown would have been unexpected. Moreover, any unexpected results must be commensurate in scope with the claims the evidence is offered to support (MPEP 716.02(d)). For example, the results shown in Table 1 were derived using a substrate peptide for active PKCα and it is unclear whether similar results would be yielded via other detection methods. An appropriate affidavit or declaration describing the results and why they are unexpected would be of probative value (see MPEP 716.01 (a)).
Applicant further cites Haraldsson as evidencing that active PKCα would likely be excluded from urine by the glomerular barrier based on its size and charge, and thus one would not have had a reasonable expectation of success. This is not persuasive proteins of a size and charge substantially similar to that of active PKCα are known to be present in urine (e.g., because glomerular function can be impaired in various disease states including cancer) (see Response to Arguments in Final Rejection of 19 Dec. 2025 and references cited therein). Evidence that one of ordinary skill would not expect to detect active PKCα in urine via the methodology used by the cited art might be persuasive to overcome the pending 103 rejections.
Claim Rejections - 35 USC § 102
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.
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.
Claim 1, 4, 6, 7, 11 and 14-23 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative (in the case of claims 4, 11, 14, 15), under 35 U.S.C. 103 as obvious over US20120329854 to Metzger et al. (cited in IDS of 22 Aug. 2022), as evidenced by Lenis et al., Jama 324.19 (2020): 1980-1991.
Regarding claim 1, Metzger teaches a method of detecting, prognosticating and/or grading cancer comprising detecting active PKCα in a sample from a subject ([0012]-[0014]; [0050]-[0053]; [0075]-[0080]; [0088]-[0095]). The sample can be a body fluid of the subject, and "Preferably, the body fluid is blood, plasma, urine, saliva, serum, semen, prostate fluid or seminal fluid" ([0120]-[0121]; [0198]; [0214]; [0226]). The subject can be suspected of suffering from cancer (i.e. be at risk of having cancer) or have cancer, e.g. wherein the cancer is graded and/or wherein detection is in a control subject known to have cancer ([0075]-[0079]; [0113]-[0116]). The cancer can be bladder cancer ([0050]; [0191]; [0209]; [0215]; [0227]). Lenis evidences that "[b]ladder cancer accounts for approximately 90% to 95% of urothelial carcinoma" (i.e. bladder cancer is a species of urothelial carcinoma) (Lenis, under Pathophysiology and Molecular Biology). The teaching of bladder cancer anticipates the recitation of urothelial carcinoma (see MPEP 2131.02, I. - teaching of a species within a genus anticipates the genus).
Regarding claims 4 and 11, wherein the cancer includes carcinoma in situ, Metzger teaches that the method can be carried out for a wide range of cancers ([0050]; [0062]-[0064]; [0191]). Thus, it would have been prima facie obvious to carry out the method of Metzger for any type of cancer, including any urothelial/bladder cancer such as carcinoma in situ.
Regarding claims 6, 7 and 19, wherein the detecting is via reacting an antibody with active PKCα, Metzger teaches that the detecting can use an antibody against the active form of PKCα ([0095]; [0107]-[0108]).
Regarding claims 6, 7 and 20, wherein the detecting is via reacting a substrate peptide with active PKCα, Metzger teaches that the detecting can involve measuring kinase activity, e.g. by measuring phosphorylation of a labeled synthetic kinase substrate ([0093]-[0094]).
Regarding claim 7, wherein "a state of the cancer is evaluated with an obtained detection result used as an index", the instant specification states that an example of using the detection result as an index is comparison of the result with a reference value, such as a value representative of a healthy subject or a known cancer patient (Published Spec. US20230030314, [0070]). Metzger teaches comparing the detection result with a control/reference value that can be derived from known cancer patient(s) or healthy subject(s) ([0113]-[0120]). Moreover, the recitation that “the obtained detection result is used as an index” can be construed to include any use of the results for diagnostic purposes. Claim 7 does not require any particular use of the result, such as comparison to a reference value or the like.
Regarding claims 14 and 15, Metzker teaches that the diagnostic method can be carried out using urine from a subject, and it would have been obvious to further carry out a step of collecting such urine from the subject to carry out the testing.
Regarding claims 16-18, Metzker teaches that the detection can be carried out with a sample from a subject known to have cancer, e.g. wherein the cancer is graded and/or wherein detection is in a control subject diagnosed with cancer ([0075]-[0079]; [0113]-[0116]).
Regarding claims 21-23, Metzker teaches that the detection can comprise contacting with an antibody that binds active PKCα in the subject's sample (see above re claims 6, 7 and 19), and further teaches that the subject can be a human, mouse or rat ([0052]-[0053]).
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.
Claims 6, 7, 20 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Metzger, as applied to claims 1, 3, 4, 6, 7, 10, 11-12, 14-18 and 19-23, in view of JP2007236388 to Katayama et al. (previously cited; citations are to English translation).
Claims 6, 7, 20 and 24 (potentially) differ from Metzger, as applied to claims 1, 3, 4, 6, 7, 10, 11-12, 14-18 and 19-23, in that: the detecting comprises reacting a substrate peptide for detecting active PKCα with the PKCα (claims 6, 7, 20); and the substrate peptide is specific for active PKCα (claim 24).
Katayama teaches a method for detecting active protein kinase Cα (PKCα) in a subject, comprising detecting active PKCα in a biological sample from the subject, which can be a urine sample, by contacting the sample with a substrate peptide that is specifically phosphorylated by active PKCα and detecting the phosphorylated peptide (p. 3, ¶1-5 under Description; p. 5, embodiments (29)-(32); p. 7, under (4)). Katayama further teaches a method of diagnosing a disease associated with PKCα activity wherein the disease can be cancer (p. 7, under (4)).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Metzger to measure active PKCα activity in urine for diagnosis of urothelial carcinoma wherein the detection is via contacting the active PKCα with a substrate peptide specific for active PKCα as taught by Katayama because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Carrying out the method of Metzger using a substrate peptide of Katayama would have led to predictable results with a reasonable expectation of success because Metzger teaches that the detection can be via measuring phosphorylation with a synthetic peptide substrate and Katayama teaches measuring active PKCα in urine using such a peptide substrate for a substantially similar diagnostic purpose as in Metzger.
Conclusion
THIS ACTION IS MADE FINAL. 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 ROBERT J YAMASAKI whose telephone number is (571)270-5467. The examiner can normally be reached M-F 930-6 PST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657
Prosecution Insights