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 .
Amendment Entry
1. Applicant’s response to the Non-Final Action mailed 6/4/25 is acknowledged (reply 10/1/25). Preliminary Amendment filed 6/23/22 is acknowledged. In the amendment filed therein claims 6, 10, and 11 were modified. While claims 1-5 and 7-8 were canceled without prejudice or disclaimer. New claims 12-16 were added. Currently claims 6 and 9-16 are pending and under consideration.
2. Objections and/or rejections not reiterated herein have been withdrawn.
Priority
3. 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.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
4. Claims 6 and 9-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
A. In claim 6, the “predicting” in step b is vague and indefinite because it is not clear as to what the staining indicators are indicative of. The claim analyzes relapse risk based on staining for a CK2α protein in the cancer cell and classifying the staining into two categories IV: nucleus staining (+, ++), with nucleolus staining (+); and V: nucleus staining (-). with nucleolus staining (+). It is not clear how the + symbols are determined or how they can be assessed. For example, in category IV what is the difference in one + verses three +, ++ positive measures? The disclosure defines the symbols on page 4 and figure 2, section 0055 and 0072, and Table 2.
The categories appear to be generated by an abstract method where an individual measures positive staining via microscopy. However, this parameter is subjective and depends on the individual viewing the slides/stain
B. Claim 11 is vague and indefinite because it is unclear if Applicant intends to claim a product (kit) or a method of using the kit. The claim recites “a kit for use in the method of claim 6”. This wording is ambiguous. It is suggested that the claim is written to clearly set forth a kit (product) or a method in order to obviate the rejection. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
5. Claims 6 and 9-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception or JE (i.e. a natural phenomenon and abstract idea) without significantly more.
The claim(s) recite(s) an in vitro method for predicting the prognosis of a cancer patient or relapse risk, wherein-said-method comprises a step of determining the staining level of CK2α in a nucleolus.
The claims include the measurement of CK2α in a nucleolus expression in cancer cells or fractions (or natural phenomenon-compositions found naturally in cells) and abstract ideas or comparison procedures (categorizing staining into measurement IV or V) to determine cancer treatment.
This judicial exception is not integrated into a practical application because predicting categories IV or V does not apply or integrate the judicial exception.
This judicial exception is not integrated into a practical application because merely thinking about the levels and predicting if the subject will have positive or negative responsiveness to relapse, is not a practical application because there is no corresponding action related to the judicial exception. That is you don’t act on the knowledge provided by the judicial exception. Additionally, evaluating staining without a clear parameter of measurement for consistency does not render the method operable.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception a claim that focuses on a judicial exceptions must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the judicial exceptions itself. See Mayo, 101 USPQ2d at 1966.
Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature/natural principles, natural phenomenon, and abstract ideas).
The analysis to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis from Alice Corp. (also called the Mayo test) for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, Prong 1 determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea and
Step 2A, Prong 2 determine whether the claim recites additional elements that integrate the exception into a practical application of the exception
If the exception is not integrated into a practical application, then proceed to Step 2B determines whether the claim as a whole amounts to significantly more than the exception.
With respect to at least claims 6 and 9-16:
The present claims are directed to a process so Step 1 is satisfied.
The present claims are directed to judicial exceptions? The judicial exception includes the natural principle of CK2α in a nucleolus with abstract analysis reading on mental processes to assess (+) indicators of staining. In other words, the claims also recite abstract ideas as limiting elements, wherein a “prediction or judgment and comparing” with respect to positive CK2α staining levels.
This has been interpreted as being abstract ideas and are insufficient to make an otherwise ineligible claims patent eligible without significantly more recited in the claim. The analyzing, comparing, detecting and predicting steps can be done by merely reviewing the data mentally and mentally identifying a patient as having positive responsiveness to a treatment. See Bilski V. Kappos 95 USPQ2d 1001 (2010).
Additionally, see Mayo Collaborative Services v. Prometheus Laboratories Inc. 101 USPQ2d 1961 (2012) at 1965, quoting Gottschalkv. Benson, 409 U.S. 63, 67 [175 USPQ 673] (1972). ("Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.").
Furthermore, the steps of a) “determining CK2α expression in the nucleolus of cancer cells” and b) predicting relapse risk as indicated by categories VI or V have been interpreted as encompassing abstract ideas/mental processes and are insufficient to make an otherwise ineligible claims patent eligible, the claims are ineligible subject matter under 35 U.S.C. 101. (Alice Corporation Pty. Ltd. v. CLS Bank International, et al.).
The claims do not integrate the JE into a practical application. The claims are directed to predictions of relapse risk based on CK2α levels (wherein predicting is a comparing or mental step measuring +, ++ staining indicators that are ambiguous), the natural phenomenon is CK2α expression, and determining or predicting do not include wet steps of analysis.
The claims merely predicts the results of a relapse wherein the JE is not necessarily integrated into a practical application. Thus step 2A is satisfied.
The next step, STEP 2B, is to determine whether the claim as a whole amount to significantly more than the exception. There is only one active method step in the clams; the step of detecting CK2α in nucleolus cells from a cancer subject.
The method step listed in the claims are broad enough such that substantially all practical applications for in vitro assaying the level of CK2α expression are encompassed. In addition, all of the additional claim elements listed are well-understood, routine, and conventional in this art. The active method steps of the claims are readily recognized in the art as routine.
For instance, the reference to Charpin et al. (EP 2472 263 A1) teaches a method for determining CK2α levels in cancer patients. Therefore, the active method steps of the present claims, detecting CK2α cancer cells from a patient and predicting a positive responsiveness to relapse are conventional, well understood and routine. These steps are the activities that a scientist would have relied upon to achieve the goals of the invention.
Additionally, claim 6 step c includes an “if clause” that indicates treatment may not occur if the patient is not found to be in category IV or V. In the instances where treatment is not performed the JE is not integrated into a practical application.
Mental steps and/or computer-implemented abstract ideas and are insufficient to make an otherwise ineligible claims patent eligible, the claims are ineligible subject matter under 35 U.S.C. 101. (Alice Corporation Pty. Ltd. v. CLS Bank International, et al).
In the instant case, detecting and comparing CK2α (i.e. natural products, proteins, or biomarkers) information regarding a sample or test subject to a normal control or target data reads on “An Idea ‘Of Itself’” as when given its broadest reasonable interpretation, such a comparison would read on a mental process that could be performed in the human mind, or by a human using pen and paper. See July 2015 Update, Quick Reference Guide.
Similar mental processes have been held by the courts to be abstract ideas, e.g., collecting and comparing known information in Classen, or comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC.
The specific information that is being compared (CK2α levels to predict relapse and treatment responsiveness) merely narrows the abstract idea, which does not make the comparison step less abstract and is not sufficient to provide eligibility on its own.
In the present claims there are no other active method steps that transform the process into an inventive application of the detecting and predicting steps.
In sum, when the relevant factors are analyzed, they weigh against the present claims amounting to significantly more than the judicial exceptions themselves. Accordingly, the claims do not qualify as eligible subject matter.
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.
6. Claim(s) 11 is/are rejected under 35 U.S.C. 102(a)(1)as being anticipated by Charpin et al. (EP 2 472 263 A1, publication date 04.07.2012 – filed on IDS 1/6/24).
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..
Regarding clam 11, [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.
Response to Arguments
Applicants arguments have been carefully considered but were not found persuasive for the following reasons: Applicant contends that the two levels of "+" and "++" in category IV and V are readily understood by the POSITA. According to the applicant, this method is very commonly employed in breast cancer diagnosis, e.g., based on histochemical staining of biomarkers such as HER2, progesterone receptor, and estrogen receptor. HER2 staining intensity (globally known as a useful criterion for diagnosing breast cancer) is commonly classified by three levels "+", "++", and "+++", and this way of classification is globally established in the art.
Therefore, applicant submits that the recitations based on two levels of "+" and "++" will be readily clear to a person skilled in the art. This argument was not found convincing because parameters for determining +, ++ as an indicator for CK2α staining to determine relapse risk is not disclosed.
7. 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.
8. For reasons aforementioned, no claims are allowed.
9. 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 schedule but can normally be reached on Monday-Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at telephone number 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Lisa V. Cook
Remsen - Hoteling
(571) 272-0816
1/10/26
/LISA V COOK/Primary Examiner, Art Unit 1642