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 .
The Response of 5 Dec. 2025 has been entered.
Claims 1, 3, 4, 6, 7, 10-12 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Any rejection not reiterated herein has been withdrawn.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 5 Dec. 2025 have been fully considered but they are not persuasive.
Applicant argues that one of ordinary skill would not have expected activated PKCα to pass into the urine because its negative charge and size would have prevented it from passing through the glomerulus. Applicant cites [0006] of the specification as well as Appx I. No appendix was submitted with the Response of 5 Dec. 2025. Nevertheless, Applicant’s arguments/assertions are found unpersuasive for the reasons below. Human PKCα of instant SEQ ID 4 has a predicted molecular weight of 77 KDa and a net charge of -6.33 (see attached Prot Pi output for SEQ ID 4, under Isoelectric Point and Molecular Mass). Pieper et al., Proteomics 4.4 (2004): 1159-1174, evidences that the normal human urine proteome includes numerous proteins having a size equal or greater than PKCα (Pieper, Fig. 1 and Table 1). For example, transferrin is found in normal urine (Pieper, Table 1, spot 17) and has approximately the same size and net charge (77 KDa and -6.8) as PKCα. In view of the above, Applicant’s argument that one of ordinary skill would not have expected PKCα to be detectable in urine because of its size and/or negative charge is not sufficient to overcome the prima facie case of obviousness based on the cited combination (including the teaching in Katayama that activated PKCα can be detected in urine). Moreover, the evidence at [0006] of the specification is considered to be unsupported arguments of counsel, and no additional supporting evidence has been offered (such as a declaration and/or supporting evidence attesting to what one of ordinary skill in the art would have believed about detectability of PKCα in urine).
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 1, 3, 4, 6, 7, 10-12, 14-18, 20 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of JP2007236388 to Katayama et al. (cites are to attached English translation) in view of Kong et al., Urology 65.6 (2005): 1228-1232 and Satyal et al., Frontiers in oncology 9 (2019): 1266.
Regarding claims 1, 6, 7, 20 and 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)). The recitation of “detecting active protein kinase Cα” in claim 1 is construed herein as including indirect detection via a substrate peptide, as such detection is described as a detection method for active PKCα in the instant specification (Published Spec. US20230030314, [0074]-[0093]) and is claimed in dependent claims 6, 7, 20 and 24.
Regarding the recitation in claim 1 that the method is “in a subject having or having a risk of cancer”, Katayama teaches a method of diagnosing a disease associated with PKCα activity wherein the disease can be cancer (p. 7, under (4)). Such a method of diagnosing cancer would inherently be conducted on a subject “having or having a risk of cancer”. Alternatively, it would have been obvious to carry out such a diagnostic method on any subject “having or having a risk of cancer”.
Regarding claim 7, the diagnosis of cancer according to Katayama can be considered “evaluating a state of cancer” as recited in claim 7 (e.g., whether the subject has or does not have a cancer). The recitation that “the obtained detection result is used as an index” is construed herein to include any use of the results of the method 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, Katayama teaches that the diagnostic method can be carried out using urine from a subject (p. 7, under (4)), and it would have thus been obvious to further carry out a step of collecting a urine sample from the subject to carry out such testing.
Claims 1, 3, 4, 6, 7, 10-12, 14-18, 20 and 24 differ from Katayama in that: the cancer includes urinary cancer (claims 1, 7); the cancer is urothelial carcinoma (claims 3, 10) or carcinoma in situ (claims 4, 11, 12); the subject is diagnosed with cancer (claim 16); and the subject is diagnosed with urinary cancer (claims 17, 18).
Kong teaches that increased levels of active PKCα are associated with tumor grade of bladder (i.e. urinary) cancer and with risk of cancer recurrence after treatment (p. 1230-1231, under RESULTS and COMMENT). Kong further teaches that “PKCα may be used as a surrogate biomarker for prognosis” of bladder cancer (p. 1232, under CONCLUSIONS). PKCα was measured using an anti-PKCα antibody in bladder tissue samples from subjects diagnosed with superficial bladder carcinoma (SBC) with transitional cell (i.e. urothelial) carcinoma (p. 1229-1230, under MATERIALS AND METHODS; see also, Spec. [0052] stating that “Urothelial carcinoma refers to cancer occurring in a cell of the mucosal urinary tract designated as urothelium (transitional epithelium)”). The patients included subjects with varying levels of cancer including stage Tis (i.e. carcinoma in situ) (Kong, p. 1229, under PATIENTS; see also, Spec., [0052] stating that “Tis is designated as carcinoma in situ”).
Satyal teaches that urine is a rich source of potential tumor biomarkers for bladder/urinary cancers because urine bathes the genitourinary organs and bladder tumors, and has benefits of ease of acquisition and availability compared to conventional tissue biopsies (p. 1-2, under INTRODUCTION TO LIQUID BIOPSY; p. 3, 1st ¶).
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 Katayama to measure active PKCα in urine for diagnosis/study of cancer wherein the cancer is urothelial carcinoma/carcinoma in situ because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Carrying out the method of Katayama for the purposes of diagnosing/studying urothelial carcinoma/carcinoma in situ would have led to predictable results with a reasonable expectation of success because Katayama teaches measuring active PKCα in urine for diagnosis/study of cancer and Kong teaches that urothelial carcinoma/carcinoma in situ is significantly associated with increased levels of active PKCα. While Kong measured PKCα in bladder tissue sample, Satyal teaches that urine is a rich source of potential tumor biomarkers for bladder/urinary cancers because urine bathes the genitourinary organs and bladder tumors. Thus, one would have had a reasonable expectation of success in applying the method of Katayama for measuring levels of active PKCα in urine to urothelial carcinoma/carcinoma in situ subjects as taught by Kong. One of ordinary skill would have been motivated to use the method of Katayama for the purposes of diagnosing/studying urothelial carcinoma/carcinoma in situ because Katayama and Kong teach that active PKCα can be useful diagnostic biomarker for bladder cancers, and Satyal teaches that urine-based testing has advantaged over traditional biopsies, including ease of access and sample availability.
With respect to claim 12 (wherein the cancer includes urothelial carcinoma and carcinoma in situ), the instant specification evidences that urothelial carcinoma can be present in a variety of stages that includes carcinoma in situ (Spec., [0052]), and Kong teaches patients having various stages of cancer including carcinoma in situ (see above).
Claims 19 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Katayama in view of Kong and Satyal, as applied to claims 1, 3, 4, 6, 7, 10-12, 14-18, 20 and 24, further in view of Kang et al., Carcinogenesis 30.11 (2009): 1927-1931, as evidenced by Anti-phospho-PKCα (Ser657/Tyr658) Antibody Upstate® (“Upstate”).
Claims 19 and 21-23 differ from the combination of Katayama in view of Kong and Satyal, as applied to claims 1, 3, 4, 6, 7, 10-12, 14-18, 20 and 24, in that: the detecting comprises reacting an antibody with the active protein kinase Cα (claim 19); and the antibody binds to a human-derived (claim 21), mouse-derived (claim 22) and rat-derived (claim 23) protein kinase Cα or a fragment thereof.
Kang teaches that activated PKCα is useful as a cancer biomarker, and that activated PKCα can be detected in a biological sample (plasma from normal and cancer model mice) using either a peptide substrate that is specifically phosphorylated by activated PKCα (as in Katayama) or using an antibody that binds activated PKCα (p. 1927, under Introduction; p. 1927-1928, under Phosphorylation of substrate with plasma sample and Western blot analysis; p. 1929-1930, under Discussion). The antibody used for the detection was the Upstate® anti-phospho-PKCα (p. 1928, under Western blot analysis).
Regarding claims 21 and 23, Upstate evidences that the antibody binds to activated PKCα derived from both rat and human (p. 3, under Species Reactivity).
Regarding claim 22, Kang teaches that the antibody binds to activated PKCα in mouse plasma samples (p. 1928, under Western blot analysis).
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 the combination of Katayama in view of Kong and Satyal to diagnose a urinary cancer by measuring activated PKCα in a urine sample wherein the activated PKCα is measured using an anti-PKCα antibody as taught by Kang because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to measure activated PKCα in the method of Katayama in view of Kong and Satyal using an anti-PKCα antibody as taught by Kang in order to provide a means for directly detecting/measuring PKCα in the sample and/or to provide a means to confirm the findings from substrate-based detection. Measuring activated PKCα in the method of Katayama in view of Kong and Satyal using an anti-PKCα antibody as taught by Kang would have led to predictable results with a reasonable expectation of success because Katayama teaches measuring PKCα using a peptide substrate, and Kang teaches that PKCα can be measured in biological samples for the same general purpose as a cancer biomarker using either a peptide substrate or an anti-PKCα antibody.
Conclusion
No claim is allowed.
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 ROBERT J YAMASAKI whose telephone number is (571)270-5467. The examiner can normally be reached M-F 930-6 PST.
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657