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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/9/26 has been entered.
Amendment Entry
2. Applicant’s response to the Final Action mailed 1/14/26 is acknowledged (reply dated 4/9/26). The amendment filed 4/9/26 is acknowledged. In the amendment filed therein claims 1 and 15 were modified. While claims 1-5, 7-8, and 11 were canceled without prejudice or disclaimer. New claims 17 was added. Currently claims 6, 9-10, and 12-17 are pending and under consideration.
3. Objections and/or rejections not reiterated herein have been withdrawn.
Priority
4. This application is a 371 of PCT/JP2020/048650, filed December 25, 2020, which claims the benefit of Japanese Patent Application No. 2019-234099, filed December 25, 2019. The priority date for the application is 12/25/19.
DECLARATION/AFFIDAVITE UNDER 1.132
5. The Declaration of Dr. Miwako Homma under 37 CFR 1.132 filed 4/9/26 is sufficient to overcome the rejection of claims 6 and 9-16 based upon 35 USC § 101.
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.
6. Claim(s) 6, 9, 10, and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Charpin et al. (EP 2 472 263 A1, publication date 04.07.2012 – filed on IDS 1/6/24) in view of Yenice et al. (The Prostate, Vol.24, No.1, pp. 11-16, 1994).
Charpin et al. disclose a method of determining the prognosis of a patient suffering from breast cancer, comprising the step of measuring the level of expression of the CK2α subunit in breast cancer cells obtained from said patient. [0007] A high CK2α expression is associated with a poor prognosis. Indeed, the data shown in the example demonstrate that a lower survival rate is obtained in the group of patients with higher CK2α expression. [0009] CK2α levels in patients with metastasis were significantly greater than those with disease free survival. A high CK2α expression is associated with a high-risk of disease recurrence and distant metastasis development.
[0015] In a further embodiment, the levels of expression of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 predictive markers are quantified in a node-negative patient together with the expression of CK2α, wherein the predictive markers are selected from the group consisting of HIF-1α, SHARP2, EIF4E, pMAPK, MMP7, pAKT, FGFR-1, pmTOR, Fyn and JAK. [0016] Typically, a method of prognosis according to the invention may be used in combination with any other methods already used for the prognostic assessment of breast cancer, including stage, demographic and anthropometric parameters, results of routine clinical or laboratory examination, including size of the tumor, histoprognostic grading, hormone receptors, oncotype, MammaPrint, uPA/PAI-1.
[0026-0028] The invention also provides a kit comprising: a) a binding partner capable of selectively interacting with CK2-α ; and b) 1, 2, 3, or 4 different binding partners which specifically bind to 1, 2, 3 or 4 respectively, predictive markers selected from the group consisting of SHARP-2, EIF4E, pMAPK, and pAKT
[0038] The researchers demonstrated that a strong quantitative CK2α immunohistochemical expression in breast carcinomas is individually a significant indicator of poor prognostic. Moreover, an immunohistochemical signature of 11 markers including CK2α accurately (86 %) well classifies node negative patients in good and poor outcome subsets. Our results indicate that CK2α evaluation together with key downstream CK2 targets would be a useful tool to identify patients at high risk of distant metastases and that CK2 can be considered as a relevant target for potential specific therapy.
Charpin et al. differ from the instant invention in not specifically teaching histochemical intensity measurements of CK2α in the nucleus and cytoplasm.
However, Yenice et al. disclose that chromatin-associated non histone protein phosphorylation, catalyzed by intrinsic protein kinase reaction in chromatin preparations from human benign prostatic hyperplasia (BPH) prostate samples was markedly elevated, compared with the normal prostate chromatin samples. And the properties of this protein kinase reaction were suggestive of the involvement of casein kinase(s). The researchers also demonstrated that this protein kinase (CK2) is present in human prostate chromatin. Its activity is increased in BPH chromatin by about 25-fold, as compared with its activity in the normal prostate chromatin. This suggests that CK-2 is a possible mediator of the enhanced phosphorylation of chromosomal proteins in BPH chromatin. By comparison, CK-2 activity in chromatin preparations from prostatic carcinoma samples was markedly less elevated than that of the BPH chromatin. Immuno-histochemical analysis of the enzyme in human frozen sections of prostate tissue samples showed that the enzyme immunostaining was diffuse in the cytoplasm, but more intense in the nucleus, especially in the nucleoli. In general, the staining corresponded with the enzymic data. See abstract and Table II page 13.
It was shown that androgen action in the rat ventral prostate evokes an association of CK-2 with nucleus and in particular with the chromatin constituents. In addition, expression of mRNA for the α and β subunits of CK-2 is androgen dependent in rat ventral prostate. Thus, it is conceivable that similar responses occur in the nuclei of BPH tissue. See page 14, 1st column, and figure 1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to measure CK2 kinase immunohistochemical intensity in the cytoplasm and nucleus as taught by Yenice et al. in the CK2α cancer methods of Charpin et al. because Yenice et al. demonstrated that protein kinase (CK2) is present in human prostate chromatin. And its activity is increased in BPH chromatin by about 25-fold, as compared with its activity in the normal prostate chromatin. This suggests that CK-2 is a possible mediator of the enhanced phosphorylation of chromosomal proteins in BPH chromatin. By comparison, CK-2 activity in chromatin preparations from prostatic carcinoma samples was markedly less elevated than that of the BPH chromatin. Immuno-histochemical analysis of the enzyme in human frozen sections of prostate tissue samples showed that the enzyme immunostaining was diffuse in the cytoplasm, but more intense in the nucleus, especially in the nucleoli. In general, the staining corresponded with the enzymic data. See abstract and Table II page 13.
One skilled in the art would have been motivated to monitor immunostaining intensity to determine cell viability and increased phosphorylation as an indicator for abnormal activity in comparison to normal samples. Absent evidence to the contrary the measurement of staining intensity in the nucleus and cytoplasm is deemed obvious.
Response to Arguments
7. Applicant's arguments filed 4/9/26 have been fully considered but they are not persuasive.
Applicants arguments have been carefully considered but were not found persuasive for the following reasons: The reference to Yenice et al. has been added to make the immunohistochemical measurement of CK2 in nucleus/cytoplasm obvious.
Allowable Subject Matter
8. Claim 17 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
9. For reasons aforementioned, no claims are allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LISA V COOK whose telephone number is (571)272-0816. The examiner works a flexible Part-Time schedule but can normally be reached on Monday, Thursday, and Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR.
Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://portal.uspto.gov/external/portal. Should you have questions about access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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.
Lisa V. Cook
Remsen - Hoteling
(571) 272-0816
7/11/26
/LISA V COOK/Primary Examiner, Art Unit 1641
Prosecution Insights